p53, HER-2/neu Oncoprotein, and DNA Analysis in Epithelial Ovarian Cancer

Lee, N W; Chang, K H; Lee, Y H; Kim, H S; Yeom, B W; Lee, K W

Abstract

Expression of mutant p53 and HER-2/neu oncoprotein is thought to be prognostic indicies in patients with epithelial ovarian cancer. DNA ploidy and SPF(S-phase fraction) are also thought to be biologic or prognostic indicies in epithelial ovarian cancer. The present study was carried out to investigate the expression and prognostic role of mutant p53, HER-2/neu oncoprotein, and DNA ploidy in epithelial ovarian cancer. Another purpose of this study was to evaluate the relationship between these molecular characteristics(HER-2/neu, p53 dncoprotein and DNA ploidy) and other prognostic factors(stage, grade, histologic type). We reviewed archival specimens from 41 patients with epithelial ovarian cancer diagnosed during the period 1988~1994. Immunohistochemistry was used to detect p53 and HER-2/neu oncoprotein expression. We used flow cytometry to calculate DNA ploidy and S-phase fraction. Kaplan-Meier method and log-rank test were used to analyze clinical and molecular data with respect to survival. The obtained results are summarized as follows: 1. Expression of p53 oncoprotein was demonstrated in 48.8% of the tumors and was associated with a 36.3% probability of 5-year survival, compared to a 67.4% probability of 5-year survival for the p53 oncoprotein negative cohort(p=0.019). 2. There was no significant relationship between overall survival and HER-2/neu oncoprotein expression. 3. Coexpression of p53 and HER-2/neu oncoprotein was associated with a 16.7% probability of 5-year survival, compared to a 66.7% probability of 5-year survival for the p53 and ER-2/neu oncoprotein negative cohort(p=0.021). 4. The percentage of p53 and HER-2/neu expression was higher in advanced ovarian cancer(stage III, IV), although statistical evaluation was not significant. p53, HER-2/neu oncoprotein expression had no correlation with tumor grade or histologic type. 5. About 58.5% of tumors were aneuploidy, which was associated with poor prognosis(p=0.042). S-phase fraction greater than 15% showed similar trends(p=0.018). It is suggested that molecular characteristics provide objective data that my be useful in predicting prognosis in patients with epithelial ovarian cancer. But further investigation of molecular and genetic characteristics are needed to refine our diagnostic and treatment modalities.