PATHOLOGY & ONCOLOGY RESEARCHVol. 13 No. 3, 2007

 Article

Relation of Neuroendocrine Cells to Transforming Growth Factor-Alpha and Epidermal Growth Factor Receptor Expression in Gastric Adenocarcinomas: Prognostic Implications

Cigdem CELIKEL1, Funda EREN2, Bahadir GULLUOGLU3, Nural BEKIROGLU4, Serdar TURHAL2

1Department of Pathology, Marmara University School of Medicine, Istanbul, Turkey
2Department of General Surgery, Marmara University School of Medicine, Istanbul, Turkey
3Department of Biostatistics, Marmara University School of Medicine, Istanbul, Turkey
4Department of Medical Oncology, Marmara University School of Medicine, Istanbul, Turkey

 

The presence of neuroendocrine (NE) cells in gastric adenocarcinoma (GCa) is well documented, however, their significance is controversial. There is no evidence in the literature concerning the possible effect of these cells on the expression of TGF-alpha and EGFR, which are believed to confer growth advantage to tumor cells. 101 partial or total gastrectomy specimens from patients operated for conventional gastric adenocarcinoma were included in the study. In each case immunohistochemistry was performed on sequential tissue sections for chromogranin A (ChrA), TGF-alpha and EGFR. Samples were graded based on the number of ChrA-positive cells (0-3). TGF-alpha and EGFR expressions were evaluated according to both the intensity (0-2) and quantification of the positively stained areas (0-3). Follow-up data was available in 54 patients. Twenty-seven patients died of disease, while 27 patients were alive with a follow-up of at least 15 months. ChrA expression was detected in 54.4% of the tumor specimens. TGF-alpha was stained positively in 42.6% and EGFR in 49.5% of the cases. NE cells in GCa was related to TGF-alpha (p<0.0001) and EGFR expression (p<0.05), and TGF-alpha/EGFR coexpression (p<0.001). Among histopathologic variables, the presence of NE cells was significantly related to grade, stage and lymph node status. Although the presence of NE cells had no effect on survival, the expression of EGFR (p<0.0001) and TGF-alpha (p=0.002) were related to survival. The results of our study suggest that the presence of NE cells may have an effect on the expression of TGF-alpha and EGFR in GCa, and the autocrine mechanism between TGF-alpha and EGFR plays an important role in the prognosis of gastric carcinoma. Pathology & Oncology Research, Vol 13, Nr 3, 215-226, 2007

Key words: neuroendocrine cells; TGF-alpha; EGFR; gastric carcinoma


Received: Nov 8, 2006; accepted: Aug 21, 2007
Correspondence: Cigdem CELIKEL, Department of Pathology, Marmara University School of Medicine, Tophanelioglu Cad. Istanbul 81190, Turkey; Tel: (90) 216 321 66 09, Fax: (90) 216 327 19 05; E-mail: turege@superonline.com.tr

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