Expression of bcl-2 is most commonly associated with the t(14;18) tran
slocation present in most follicular lymphomas (1). More recently, bcl
-2 oncoprotein has been identified in normal tissues and in nonhematol
ogic malignancies. In this study, we investigate the use of bcl-2 as a
marker to distinguish metastatic breast carcinoma from primary lung a
nd gastric cancers, and we evaluate the role of bcl-2 as an independen
t prognostic factor in breast carcinoma and its relationship to other
breast cancer markers, bcl-2 immunostains were done on 371 adenocarcin
omas of the breast, lung, and stomach, Additionally, 231 samples of me
tastases from patients with breast or gastric cancer were evaluated fo
r bcl-2 expression, All breast cancer tissue samples had immunohistoch
emical data on expression of estrogen and progesterone receptors, p53,
neu/c-erb2, and MIB-1. A large proportion (79.3%) of invasive breast
carcinomas expressed bcl-2, whereas only 5.6% and 8.3% of pulmonary an
d gastric carcinomas did, Moreover, staining was moderate to intense i
n 70.2% of the breast cancers, compared with only one specimen of lung
carcinoma (1.9%) and gastric carcinoma (0.9%) that showed moderate st
aining. There was agreement of bcl-2 expression between primary and me
tastatic sites in all specimens except one, Expression of bcl-2 in bre
ast adenocarcinomas was significantly associated with hormone receptor
positivity and low histologic grade. Nonetheless, 20.6% of bcl-2-posi
tive specimens were estrogen receptor negative and 24.2% of bcl-positi
ve specimens were progesterone receptor negative. Neither the presence
nor the absence of bcl-2 expression significantly predicted disease-f
ree survival or overall survival in patients with breast cancer. We co
nclude that adenocarcinomas with intense bcl-2 staining are more likel
y to be of breast than of pulmonary or gastric origin. We recommend th
e addition of bcl-2 to a panel of antibodies (estrogen receptor, GCDFP
-15, and 5100) that might contribute to the identification of a larger
proportion of metastatic breast carcinomas, because almost one-half o
f the estrogen-receptor negative cancers were bcl-2 positive.