Evaluation of clinical significance of TP53, BCL-2, BAX and MEKI expression in 229 ovarian carcinomas treated with platinum-based regimen

Abstract

In cell line studies, BCL-2, BAX, as well as novel MEKI protein levels have strong influence on ovarian cancer response to cisplatin-based chemotherapy. However, such associations have not been demonstrated clinically. We evaluated prognostic/predictive significance of these proteins with regard to TP53 status. Immunohistochemical analysis was performed on 229 ovarian carcinomas FIGO stage IIB-IV treated with platinum-based chemotherapy; the results were analysed by the Cox and logistic regression models. Clinical parameters (residual tumour size, patient age, FIGO stage) were the only indicators of overall survival (OS) and the strongest predictors of complete remission (CR). On the other hand, BAX expression was the strongest (P = 0.005) or the only (in FIGO IIIC, P = 0.02) prognostic indicator of disease-free survival (DFS) in the TP53(+) group. TP53(+) and TP53(-) ovarian carcinomas differed in clinical and molecular prognostic and predictive factors. Another novel finding is that CR was negatively influenced by high BAX expression in all patients group (P = 0.047) and by BCL2 expression in the TP53(-) group (P = 0.05). High MEKI expression was associated with endometrioid and clear cell carcinomas (P = 0.049); its loss was found with advancing FIGO stage (P = 0.002). Our results suggest that binomial TP53 status divides ovarian carcinomas into two biologically distinct groups. BAX expression is an important factor of DFS in the TP53(+) group. BCL-2 and BAX, but not MEKI expressions have predictive value in ovarian cancer patients treated with platinum-based chemotherapy. © 2003 Cancer Research UK.