Expression of apoptosis-related proteins is an independent determinant of patient prognosis in advanced ovarian cancer

Purpose: The present study was undertaken to investigate the prognostic and predictive relevance of the expression of apoptosis-related proteins Bax, Bcl-X-L, and Mcl-1 in advanced ovarian cancer. Patients and Methods: Tumor biopsies from 185 consecutive and homogeneously treated patients with stage III ovarian cancer were examined immunohistochemically for the expression of Bax, Bcl-X-L and Mcl-1 proteins. Their prognostic relevance wets examined in a uni- and multivariate survival analysis. Results: Sixty-six percent of cancer cases expressed sox, 62% Bcl-X-L, and 53% Mcl-1. The expression of Bax correlated with tumor differentiation (P =.016) and less residual disease after surgery (P <.0001). In univariate analysis, Bax expression was associated with improved (P =.0004) prognosis and Mcl-1 expression with poorer (P =.011) prognosis. None of the factors studied was of independent prognostic significance by itself, but when Bax and Bcl-2 expression data were considered together, this combined variable was of independent prognostic significance (P =.0115), together with residual disease status (P =,0016), differentiation grade (P =.0014), and the presence of ascites (P =.0122). Patients with a long median survival (104 months) could be discriminated from those with a short one (16 months) by combining the individual patients' expression data for p53, Sox, and Bcl-2 with their residual disease status [P <.00001). None of the factors studied wets able to predict response to chemotherapy Conclusion: The expression of selected apoptosisrelated proteins is of independent prognostic significance and may be helpful in a molecular substaging of patients with stage III ovarian cancer, (C) 2000 by American Society of Clinical Oncology.