Cytometric analysis of Fas and Bcl-2 expression in normal prostatic epithelium and prostate cancer

The apoptosis-inducer Fas and the apoptosis-suppresser Bcl-2 are members of the tumor necrosis factor receptor and Bcl-2 gene superfamilies, respectively. Bcl-2 is overexpressed in hormonally refractory prostate cancer. Fas is expressed in several prostatic carcinoma cell lines but its in vivo expression in normal prostate and in prostate cancer is poorly understood. Formalin-fixed tissue sections from 10 benign prostatic hyperplasias, 10 low-grade and 10 high-grade organ-confined prostate cancers, and 6 metastatic prostate cancers were evaluated for immunoreactivity with Fas and Bcl-2 monoclonal antibodies. In addition, Fas expression was quantitated by computerized cytometry. The results were compared by one-way analysis of variance followed by Bonferroni tests. In benign prostate samples, Bcl-2 and Fas were expressed on basal cells and secretory cells, respectively. Bcl-2 was not expressed in any organ-confined tumors and only in one of six metastatic tumors (17%). Fas was expressed in all organ-confined tumors and in two of six metastatic tumors (33%). Fas expression was significantly decreased (P < 0.001) in prostate cancer (0.20 pg/cell) compared with benign prostate (0.79 pg/cell). The decrease was inversely related to the malignant grade of the tumors (0.30 pg/cell in low-grade tumors, 0.19 pg/cell in high-grade tumors, and 0.003 pg/cell in metastatic tumors). Based on these preliminary data, decreased expression of Fas appears to be an early molecular event in prostate cancer. The decline begins in low-grade tumors. The lowest expression occurs in metastatic carcinomas, which are often Fas negative. Overexpression of Bcl-2 appears to be a later and unrelated molecular event. Both abnormalities may be implicated in tumor progression by prolonging tumor cell survival.