HER-2 NEU, P53, AND DNA ANALYSES AS PROGNOSTICATORS FOR SURVIVAL IN ENDOMETRIAL CARCINOMA/

Objective: To compare the prognostic importance of certain molecular b iologic characteristics (HER-2/neu and p53 gene overexpression, DNA pl oidy, and the S-phase fraction) to standard clinical-pathologic factor s used to predict survival in patients with endometrial carcinoma. Met hods: We reviewed archival specimens from 128 patients with endomehial cancer diagnosed during the period 1985-1987. One hundred four cases were eligible for inclusion in the study. Immunohistochemistry was use d to detect p53 and HER-2/neu overexpression. We used flow cytometry t o calculate DNA ploidy and the S-phase fraction. Life-table analysis a nd Cox multiple regression were used to analyze clinical and molecular data with respect to survival. Results: International Federation of O bstetrics and Gynecology stage, nuclear grade, lymph-vascular space in vasion, and adverse histopathologic features each significantly correl ated with poor outcome (each at P less than or equal to .001). Overexp ression of p53 was demonstrated in 15% of the tumors and was associate d with a 12% probability of 5-year survival, compared to a 90% probabi lity of 5-year survival for the p53-negative cohort (P = .0001). Thirt y percent of the tumors were aneuploid, which was also associated with poor prognosis (P = .0003). HER-2/neu overexpression and an S-phase f raction greater than 10% showed similar trends, but were not statistic ally significant. On multivariate analysis, p53 overexpression was the strongest independent prognosticator of survival (P = .0001). Conclus ion: Molecular characteristics provide objective data that may be usef ul in predicting prognosis in patients with endometrial canter. Furthe r investigation of molecular and genetic characteristics are needed to refine our diagnostic and treatment modalities.