PATHOLOGY & ONCOLOGY RESEARCHVol. 7 No. 3, 2001

 Article

Expression of erbB/HER Receptors, Heregulin and P38 in Primary Breast Cancer using Quantitative Immunohistochemistry

Francisco J ESTEVA1, Gabriel N HORTOBAGYI1, Aysegul A SAHIN2, Terry L SMITH3, Dot Mon CHIN4, Shang-Ying LIANG3, Lajos PUSZTAI1, Aman U BUZDAR1, Sarah S BACUS4

1Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, USA
2Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, USA
3Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, USA
4Quantitative Diagnostics Laboratory, Elmhurst, USA

 

The purpose of this study was to investigate the frequency of expression of the erbB/HER family of growth factor receptors, their ligand heregulin, and the two different signaling pathways p38 and mitogen-activated protein kinase (MAPK), as well as the status of HER-2 phosphorylation in tumor specimens from patients with primary breast cancer. The level of expression of these proteins was measured by quantitative immunohistochemistry combined with microscope-based image analysis in paraffin-embedded breast cancer tissue from 35 patients. The frequency of expression was: EGFR (51%), HER-2 (54%), P-HER-2 (48%), HER-3 (48%), HER-4 (57%), heregulin (48%), p38 (17%), MAPK (48%). There was evidence of associations among the coexpression of heregulin, EGFR, HER-2, and HER-3. Also, there was evidence of a positive association between P-MAPK and HER-4. HER-3 was expressed at high levels in patients younger than 50 years of age. There was a trend for expression of higher levels of HER-4 in tumors larger than 2 cm. The expression of EGFR, HER-2, heregulin, p38 and MAPK was independent of age, tumor size, number of lymph nodes involved or hormone receptor status. The HER family of growth factor receptors appear to be regulated independently in invasive breast cancer. Assessing the expression of multiple tumor markers by quantitative immuno-histochemistry is feasible. Further research is needed to determine the prognostic and predictive roles of the various associations between HER receptors, their ligands and signal transduction molecules in patients with early-stage breast cancer. Pathology & Oncology Research, Vol 7, Nr 3, 171-177, 2001

Key words: Tumor markers; biological; proto-oncogene proteins; immunohistochemistry; ligands; breast neoplasm


Received: Jun 27, 2001; accepted: Jul 20, 2001
Correspondence: Francisco J ESTEVA, Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard Houston 77030-4095, USA; Tel: (713) 792-2817, Fax: (713) 794-4385

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