Overexpression of the oncogene c-erbB-2 (HER2/neu) in ovarian cancer: a new prognostic factor.

Ovarian cancer is the leading cause of death in gynecological cancers. To date, there are no prognostic factors in ovarian cancer that adequately account for tumor biology and the course of the disease. In recent years, some reports have described the prognostic significance of the amplification and overexpression of the oncogene c-erbB-2 (HER2/neu) in various human cancers, including ovarian cancer. The c-erbB-2 proto-oncogene is located on the long arm of chromosome 17. It encodes a 185 kD transmembrane glycoprotein receptor (p185HER2) that has sequence similarities with the epidermal growth factor receptor (EGF-R). In ovarian cancer, the percentage of c-erbB-2 positive cases varies from 9 to 32%. Correlation with tumor stage and the degree of histological differentiation was not observed. The overexpression of c-erbB-2 is a new and statistically independent prognostic factor. The overexpression of oncogene c-erbB-2 in ovarian cancer can-be detected by immunohistochemistry staining for the protein p185 and characterizes a group with unfavorable tumor biology and a significantly worse prognosis. Elevated serum levels of the c-erbB-2 oncoprotein have been identified in patients with various cancers known to overexpress the c-erbB-2 oncogene. The detection of a p185 oncoprotein fragment in the sera of ovarian cancer patients was recently published by our group. Antiproliferative effects of monoclonal antibodies directed against p185 have been demonstrated in breast cancer patients. This may lead to a new approach in ovarian carcinoma therapy, too, over and above the diagnostic aspects.