title: Clinicopathologic analysis of bcl-2 immunostaining in breast carcinoma.
abstract: Tissue sections of 81 breast carcinomas and 19 benign breast tissues were immunostained with a monoclonal antibody to the bcl-2 gene product, a cytoplasmic protein that regulates apoptosis. The degree of immunoreactivity 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 benign 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 cells. Neoplastic epithelial bcl-2 immunoreactivity was negative or minimally positive (staining in 1-5% of cells) in 42% of cases, heterogeneous (staining in 6-30% of cells) in 27% of cases, and diffuse (> 30% of cells) in 31% of cases. Immunostaining for bcl-2 correlated with the presence of estrogen receptor (bcl-2 negative, 16% estrogen receptor positive versus bcl-2 positive, 88% estrogen receptor-positive; P < 0.001), with differentiation (bcl-2 negative, 62% poorly differentiated versus bcl-2 positive, 8% poorly differentiated; P < 0.001) and with better disease-free survival (bcl-2 negative, 82% recurrence versus bcl-2 positive, 28% recurrence; P = 0.0001; 52-mo mean follow-up). Immunostaining 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 recurrence correlated with p53 staining, which was observed in 51% of tumors that relapsed versus only 22% of tumors that did not recur. We conclude that bcl-2 is expressed in benign breast tissues that retain proliferative capacity and partial differentiation. Moreover, in neoplastic breast tissue, it is better correlated with a differentiated, "hormonally responsive," prognostically favorable phenotype than with disabled p53 gene function.
authors.affiliation: Department of Pathology, Harper Hospital, Detroit, MI 48201, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Visscher
authors.forename: F
authors.initials: F
authors.lastname: Sarkar
authors.forename: P
authors.initials: P
authors.lastname: Tabaczka
authors.forename: J
authors.initials: J
authors.lastname: Crissman
mesh_terms: D001941:Breast Diseases / Q000473:pathology; D001943:Breast Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D002467:Cell Nucleus / Q000276:immunology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53