Breast Neoplasms/metabolism* ; Breast Neoplasms/pathology* ; Carcinoma in Situ/metabolism* ; Carcinoma in Situ/pathology* ; Carcinoma, Ductal, Breast/metabolism* ; Carcinoma, Ductal, Breast/pathology* ; Female ; Humans ; Middle Aged ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism
Abstract
To evaluate the prognostic significance of bcl-2, we investigated the correlation of bcl-2 expression with the established indicators of prognosis and tumor behavior in breast cancer. This study included a patient group of 91 histologically diagnosed female breast carcinomas. To determine the bcl-2 immunoreactivity, we used a monoclonal antibody directed against the bcl-2 protein by immunohistochemistry from paraffin-embedded tissue in a series of 91 women with breast cancer. Interpretable DNA histograms were obtained from 84 patients. The median age at diagnosis was 45.5 years and the median follow-up time was 30.5 months. Forty-eight (52.7%) cancers showed the bcl-2 immunoreactivity in the cytoplasm. The nonneoplastic portion of ductal epithelial cells and normal lymphocytes were usually stained with bcl-2 antibody. Estrogen receptors (ER)(p < 0.001) and progesterone receptors (PR)(p < 0.001) showed strong positive correlation with bcl-2 immunoreactivity. The histologic grade (p < 0.05) and nuclear grade (p < 0.01) also showed positive relationships with bcl-2 positivity but tumor size (p > 0.05) and DNA ploidy (p > 0.05) were not related with it. The bcl-2 positive patients showed longer survival (p < 0.05) compared to bcl-2 negative tumors in univariate analysis (Kaplan-Meier life table analysis). Using multivariate analysis with Cox regression, bcl-2 (p > 0.05), nuclear grade (p > 0.05), ER status (p > 0.1) and PR status(p > 0.1) were not reliable indicators for overall survival except histologic grade (p < 0.05). Our results suggest that bcl-2 expression may be related to hormonal regulation and tumor differentiation in breast carcinoma. Larger patient study groups with a longer follow-up period will be helpful to clarify the prognostic significance of bcl-2.