Prevalence and significance of HER-2/neu expression in early epithelial ovarian cancer

BACKGROUND: Although expression of the HER-2/neu oncogene may be of some prognostic importance in advanced ovarian cancer, its role in early-stage disease has not been established. The current study examined the prevalence and significance of HER-2/neu expression in early epithelial ovarian cancer. METHODS: The authors analyzed the expression of HER-2/neu on frozen tumor specimens from 40 patients with early epithelial ovarian cancer using the indirect immunoperoxidase technique with monoclonal antibodies that detect epitopes on the extracellular domain of the HER-2/neu protein. All patients underwent comprehensive surgical staging. HER-2/neu expression was graded as negative, weak, moderate (1+ to 2+), or strong (3+). Complete clinical data and long-term follow up were available for all patients. RESULTS: The distribution of patients by stage was as follows: Stage IA, 6; IB, 0; IC, 14; IIA, 4; IIB, 6; IIC, 10. The mean patient age was 53 years. Fourteen patients had serous tumors; nine, endometrioid; eight, clear cell; eight, mucinous; and one, undifferentiated. Intratumoral heterogeneity of HER-2/neu expression was observed with most specimens. In eight specimens (20%), some areas of the tumor showed strong (3+) expression, beyond the level that can be seen in normal ovarian epithelium. Twenty-eight specimens (70%) showed moderate (1+ to 2+) staining, whereas four specimens (10%) showed negative or weak staining. At a mean follow-up time among surviving patients of 32 months, 15 patients (37%) have had cancer recurrence. No statistically significant relationship was found between HER-2/neu expression and survival, disease-free survival, stage, or grade. A significant increase was found in 3+ expression of HER-2/neu in clear cell tumors. CONCLUSION: Consistent HER-2/neu overexpression occurs infrequently in early ovarian cancer, making it unlikely that such overexpression is a general early event in ovarian carcinogenesis. HER-2/neu expression does not appear to be a strong prognostic marker in early epithelial ovarian cancer.