Detection of the apoptosis-suppressing oncoprotein bcl-2 in hormone-refractory human prostate cancers

The oncoprotetn encoded by bel-2 is unique because of its intracellular location (a mitochondrial membrane protein) and apparent mode of action (suppression of apoptosis). To date, this oncogene has been associated only with the development of certain forms of human B-cell lympboma. In this report, we describe our experience with a monoclonal antibody made against a synthetic peptide for bcl-2 that can recognize the bcl-2 protein and identify cells in human prostate glands expressing this proto-oncogene with in situ immunohistochemical procedures. These procedures were utilized to survey a series of 62 human tissues to evaluate whether bcl-2 might bave a role in the developing prostate gland or in prostate oncogenesis. While all primordial epithelial cells in a fetal prostate gland immunostain for bcl-2, normal and hypertrophic prostate glands of the adult show bcl-2 expression restricted to the basal cells. All epithelial cells in areas of prostatic intrepithelial neoplasia were stained by this antibody, as were most (62%) localized invasive prostatic carcinomas. In contrast, all primary prostatic carcinomas and metastases obtained from metastatic prostate cancer patients after hormone treatment (hormone-refractory tumors) stained positive for bcl-2. This study demonstrates that the oncoprotein encoded by bel-2 can be detected at sequential stages in the natural history of human prostate cancer. Since the bel-2 oncoprotein is known to suppress the cellular response to apoptotic stimuli, it will be important to determine whether bel-2 expression is a factor in the development of prostate cancers and in the survival of hormone-refractory prostate cancer cells.