Expression of Bcl-2 and the antiapoptotic BAG family proteins in ovarian cancer.

ABSTRACT

In epithelial ovarian cancer (EOC), literature on the prognostic value of B-cell lymphoma 2 (Bcl-2) is limited and inconsistent. Little is known about the expression patterns and the prognostic value of prosurvival proteins of the Bcl-2-associated athanogene (BAG) family proteins interacting with Bcl-2. The major aim of this study was to further define the expression pattern and the prognostic role of Bcl-2 together with BAG-1, BAG-3, and BAG-4 proteins in EOC patients receiving platinum/taxane-based chemotherapy. A tissue array was constructed comprising 63 EOC patients. The expression and the prognostic value of Bcl-2, BAG-1, BAG-3, and BAG-4 in EOC were evaluated by immunohistochemistry and multivariate analysis. A positive cytoplasmic staining for Bcl-2 was observed in 23.8% of EOC samples and in all histologic subtypes. BAG-1, BAG-3, and BAG-4 were detected in tumor cell nuclei and cytoplasm. Interestingly, all patients presenting with a positive Bcl-2 staining showed additional positive nuclear and cytoplasmic BAG-4 expression (P=0.014). Expression of Bcl-2, or the BAG family proteins, independent of nuclear or cytoplasmic localization, had no significant impact on either disease-free or overall survival, both in univariate and multivariate survival analyses with the limitation of a small cohort of cases. In this study, no association between Bcl-2 expression in EOC tumor tissue and prognosis was found. Similarly, nuclear and cytoplasmic expression of the prosurvival proteins of the BAG family had no significant impact on patients' outcome.