The extent of apoptosis is inversely associated with bcl-2 expression in premalignant and malignant breast lesions.

Abstract

In this study we investigated the extent of apoptosis in benign, premalignant and malignant breast lesions and its association with the immunohistochemical expression of bcl-2 oncoprotein. In order to detect apoptotic cells and bodies in tissue sections, the 3'-end DNA labelling method was used. Immunohistochemical staining was performed by using the avidin-biotin-peroxidase complex technique. A monoclonal antibody against bcl-2 oncoprotein was used and the specificity of the antibody was confirmed by immunoblot analysis. According to the results the extent of apoptosis, as determined by the apoptotic index, was lowest in benign ductal hyperplasias and sclerosing adenoses (0.15% and 0.07%, respectively). It was moderately elevated in atypical hyperplasias and in-situ carcinomas (0.20% and 0.40%, respectively) and highest in invasive carcinomas (0.76%). In ductal invasive carcinomas, grade I lesions showed a lower apoptotic index (0.52%) than grade II (0.72%) and grade III (1.17%) carcinomas. The apoptotic index was not significantly lower in lobular (0.82%) than in ductal invasive carcinomas (0.85%). bcl-2 immunohistochemistry was inversely related to the apoptotic index. In all cases studied the inverse association was very strong (P = 0.0004) but it was also present when only carcinomas were analysed (P = 0.01). In benign and atypical hyperplasias, bcl-2 positivity was observed in all cases, but such cases were less frequent in in-situ lesions and in invasive carcinomas. The results show that there is an inverse relationship between the extent of apoptosis and bcl-2 expression in breast lesions suggesting that its expression affects the regulation of apoptosis in them.