CLINICOPATHOLOGICAL ANALYSIS OF BCL-2 IMMUNOSTAINING IN BREAST-CARCINOMA

Tissue sections of 81 breast carcinomas and 19 benign breast tissues w ere immunostained with a monoclonal antibody to the bcl-2 gene product , a cytoplasmic protein that regulates apoptosis. The degree of Immuno reactivity was then compared with clinicopathologic parameters and to immunostaining for mutated p53 gene product. Immunoreactivity for bcl- 2 was present consistently in lymphocyte populations and in residual b enign lobules. Apocrine metaplasia (n = 6) and lactating breast (n = 1 ) exhibited minimal bcl-2 expression, whereas duct hyperplasia (n = 10 ) showed staining of cells primarily at the periphery of the Involved structure and adenosis (n = 7) displayed staining in a majority of cel ls. Neoplastic epithelial bcl-2 immunoreactivity was negative OF minim ally positive (staining in 1-5% of cells) in 42% of cases, heterogeneo us (staining in 6-30% of cells) in 27% of cases, and diffuse (>30% of cells) in 31% of eases. Immunostaining for bcl-2 correlated with the p resence of estrogen receptor (beta negative, 16% estrogen receptor pos itive versus bcl-2 positive, 88% estrogen receptor-positive; P < 0.001 ), with differentiation (bcl-2 negative, 62% poorly differentiated ver sus bcl-2 positive, 8% poorly differentiated; P < 0.001) and with bett er disease-free survival (bcl-2 negative, 82% recurrence versus bcl-2 positive, 28% recurrence; P = 0.0001; 52-mo mean follow-up). Immunosta ining for p53 in greater than 5% of tumor cells was observed In 39% of cases and was more frequent in bcl-2-negative tumors (18/35, 51%) as opposed to bcl-2-positive tumors (14/46, 30%); P = NS. Disease recurre nce correlated with p53 staining, which was observed in 51% of tumors that relapsed versus only 22% of tumors that did not recur. We conclud e that bcl-2 is expressed in benign breast tissues that retain prolife rative capacity and partial differentiation. Moreover, in neoplastic b reast tissue, it is better correlated with a differentiated, ''hormona lly responsive,'' prognostically favorable phenotype than with disable d p53 gene function.