EXPRESSION OF BCL-2 IN PRIMARY BREAST-CANCER AND ITS CORRELATION WITHTUMOR PHENOTYPE

Background: The role of apoptosis (programmed cell death) in the devel opment and progression of breast cancer is unknown. Recently the bcl-2 gene has been shown to block apoptosis and thus may promote tumour de velopment. BCL-2 is localised to the luminal cells of the normal breas t, which are considered to be the origin of malignant breast disease. Patients and methods: Immunocytochemistry using anti bcl-2- antibody w as performed on 107 breast cancer specimens belonging to node-positive patients from the Ludwig Breast Cancer Studies I-IV and the results w ere correlated with survival, tumour grade, S-phase, oestrogen and pro gesterone receptor status and c-erb B-2 expression. Western and Southe rn blotting together with immunofluorescence were performed on the bre ast cancer cell lines BT-20, BT-474, MDA-MB-361, T47-D and MCF-7. Resu lts: In the breast cancer derived cell line MCF-7 BCL-2 is expressed t o a level similar to that of the B-lymphoma cell line Karpas 231 with t(14;18)(q32.3; q21.3), but no evidence of a rearrangement or gene amp lification was identified. In a study of 107 breast cancers from the I nternational Breast Cancer Study Group Trials I-IV we have demonstrate d a very significant inverse correlation of BCL-2 with c-erbB-2 expres sion (p = 0.002), and a positive correlation with oestrogen receptors (p = 0.001) and progesterone receptors (p = 0.05). In this study there was no correlation of expression with S-phase fraction in the tumours or with any stage in the cell cycle as assessed in MCF-7 cells. Concl usion: We conclude that BCL-2 might contribute to the malignant phenot ype of breast cancer by modulation of biological behaviour of cancer c ells.