BCL-2 IMMUNOREACTIVITY IN BREAST-CARCINOMA CORRELATES WITH HORMONE-RECEPTOR POSITIVITY

The protein encoded by the Bcl-2 proto-oncogene has been shown to inhi bit programmed cell death and has been primarily studied in hematolymp hoid malignancies. Recent work has elucidated Bcl-2 expression in nonh ematolymphoid malignancies of the lung, prostate, and nasopharynx. Stu dies of Bcl-2 expression in prostate carcinoma have suggested that its expression may be related to hormonal control. To determine its prese nce and possible significance in breast carcinoma, a malignancy in whi ch therapy is influenced by hormone receptor status, we used a monoclo nal antibody directed against the Bcl-2 gene product to examine Bcl-2 immunoreactivity in a series of paraffin-embedded primary breast tumor s. Benign breast tissue showed Bcl-2 positivity in the basal layer and in superficial cells. Twenty-four of 41 (58%) carcinomas were Bcl-2 p ositive. Staining for Bcl-2 was equivocal in two cases. We identified a strong correlation between Bcl-2 expression and hormone receptor pos itivity as 23 of 24 (36%) cases that were Bcl-2 positive were estrogen receptor (ER) positive (p = 0.0001) and 21 of 24 (87.5%) were positiv e for progesterone receptor PR (P = 0.0001). Of 15 Bcl-2-negative case s, 14 (93%) were ER negative and all were PR negative. One case of muc inous carcinoma was ER positive and Bcl-2 negative. Grade 1 and 2 tumo rs (Scarff-Bloom-Richardson scale) were almost three times as likely, to be Bcl-2 positive (90%) as grade 3 tumors (33%) (P = 0.0057). Bcl-2 reactivity appears to be more prevalent in well-differentiated tumors , suggesting that its presence may diminish with loss of differentiati on, a hypothesis tat is further supported by a subset of cases that we re ER negative, Bcl-2 negative, and of poor histological grade. These may be tumors that do not require Bcl-2 inhibition of apoptosis and re spond to hormonally independent proliferation factors. Our findings su pport the hypothesis that Bcl-2 expression may be related to hormonal regulation in breast carcinoma.