Clinical significance of apoptosis-related factors p53, Mdm2, and Bcl-2 inadvanced ovarian cancer

Purpose: To investigate the prognostic and predictive relevance of p53, Mdm 2 and Bcl-2 protein expression in advanced ovarian cancer. Patients and Methods: Tumor biopsy specimens from 185 consecutive and homog eneously treated patients with stage III ovarian cancer were examined immun ohistochemically for expression of p53, Mdm2, and Bcl-2 proteins, both uni- and multivariate analyses of prognostic factors were performed, and correl ations with classical clinicopathologic parameters and response to chemothe rapy were examined, Results: Forty-nine percent and 39% of cases were considered positive for e xpression of p53 and Bcl-5 respectively. p53 expression war correlated with loss of histologic differentiation and Bcl-2 expression with smaller resid ual disease after primary surgery. The absence of p53 expression and the pr esence of Bcl-2 expression were associated with improved survival but not w ith overall response to chemotherapy, although a positive correlation was f ound between Bcl-2 expression and the possibility of obtaining a completely negative second-look laparotomy. Expression of Mdm2 was found in 17% of ca ses. Although correlations were found with known favorable clinicopathologi c factors, no prognostic significance was demonstrated for Mdm2 in this pat ient group. In multivariate analyses, histologic type, degree of differenti ation, residual disease, and p53 alone or combined with Bcl-2 expression we re found to be independently associated with overall survival. Conclusion: p53, and especially the combination of p53 and Bcl-2 expression data, represents an independent prognostic predictor in stage HI ovarian c ancer. Despite their role in the apoptotic process, p53 and Bcl-2 do not se em to be clinically useful predictors of response to combination chemothera py in these patients, (C) 1999 by American Society of Clinical Oncology.