Bcl-2 expression in male breast carcinoma

Background: In female breast carcinoma (FBC), BCL2 expression is negatively correlated with tumour size, histological grade, p53 protein expression and proliferative activity, while positively correlated with estrogen and progesterone receptor positivity and patients survival. Aim: We investigated BCL2 expression in a series of male breast carcinomas (MBC) in relationship with pathological and biological features and survival. Materials and methods: Thirty-four primary MBC were retrospectively analysed. All were invasive ductal carcinomas; 21 grade 2 and 13 grade 3; 8 stage pT1, 15 pT2 and 11 pT3-4; 20 stage N0 and 14 N1-3. The mean age of the patients was 62 years; they all received radical or modified radical mastectomy. The mean follow-up period was 60.2 months. BCL2 protein was immunohistochemically detected on formalin-fixed, paraffin-embedded tissues using the monoclonal antibody anti human BCL2 oncoprotein and the LSAB method. Positive tumour cells were quantified for each case by evaluating at least 2000 cells from 10 selected areas. On serial sections, cell proliferative activity was assessed by the analysis of the argyrophilic nucleolar organizer regions (AgNORs) and the monoclonal antibodies PCNA-PC10 and MIB-1; estrogen and progesterone receptors were detected with monoclonal antibodies ER-ICA and PGR-ICA, and DNA content was assessed by flow cytometry. Chi-square test, ANOVA, Pearson’s correlation coefficient, uni- and multivariate survival analysis were used for statistics. Results: All carcinomas showed a strong BCL2 immunostaining in the cytoplasm of tumour cells. The mean BCL2 scores for the whole series were 53% (median: 49.5%; SD: +27.3%; range: 1.5-98.2%) and were significantly higher in tumours without necrosis or lymphocytic infiltration and in cases with low mitotic counts (p<0.05). No association was found with any other clinicopathological feature, although BCL2 scores were higher in node negative than in positive cases, in grade 2 than in grade 3 tumours, in diploid than in aneuploid cases, in PGR positive than in negative cases and in p53 negative than in p53 positive cases. Also, no correlation was found between BCL2 expression and AgNOR counts, MIB-1 and PCNA scores and survival. In univariate analysis, histological grade (p=0.006), DNA content (p=0.03), p53 immunoreactivity (p=0.0004), AgNOR counts (p=0.001), MIB-1 (p=0.001) and PCNA scores (p=0.002) were correlated with patients survival. In the multivariate analysis, only p53 scores (Chi-square=10.96; p=0.001) and AgNOR counts (Chi-square=5.3; p=0.02) retained independent prognostic significance. Conclusion: BCL2 protein is highly expressed in MBC; but, contrary to FBC, it is not associated with any clinicopathological feature or survival. This characteristic, together with the high prognostic significance of cell proliferative activity and the lack of prognostic significance of the hormone receptor status found in MBC, further supports the hypothesis that MBC is biologically different from FBC.