Expression of HER2 and EGFR Proteins in Advanced Stage High-grade Serous Ovarian Tumors Show Mutual Exclusivity

Human epidermal growth factors play an important role in ovarian carcinogenesis and are evaluated for prognostic and possible therapeutic roles in high-grade serous ovarian malignancies. The present study was undertaken to evaluate the expression of human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR) in advanced stage serous carcinoma and their influence on prognosis. The expression of HER2 and EGFR was studied in 59 cases of stage III and IV ovarian serous carcinomas by immunohistochemistry and fluorescent in situ hybridization. Of the 48 interpretable tumors for HER2, 6 tumors (12.5%) were scored as positive, 14 (29%) as equivocal and 28 tumors (58.5%) were negative by immunohistochemistry, while only 2/48 (4%) showed frank amplification by fluorescent in situ hybridization with ≥4 copies per cell. HER2 gene expression measured by quantitative polymerase chain reaction had good positive correlation with both protein expression and gene amplification. Although EGFR expression was seen in 32% of tumors, none of the tumors positive for HER2 protein or gene amplification had co-expression of EGFR indicating mutual exclusivity of their expression. Gene expression of both proteins also confirmed their inverse correlation (Pearsons CC=-0.15, P=0.3). Further there was no influence of protein or gene expression of these markers on the overall survival. In conclusion, HER2 and EGFR are expressed in a small percentage of tumors and the mutual exclusivity of these markers precludes the possibility of dual targeting with anti-HER2 and anti-EGFR therapy in advanced stage high-grade serous ovarian carcinoma.