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, respectiv ely. Bcl-2 is overexpressed in hormonally refractory prostate cancer. Fas i s expressed in several prostatic carcinoma cell lines but its in vivo expre ssion in normal prostate and in prostate cancer is poorly understood. Forma lin-fixed tissue sections from 10 benign prostatic hyperplasias, 10 low-gra de and 10 high-grade organ-confined prostate cancers, and 6 metastatic pros tate cancers were evaluated for immunoreactivity with Fas and Bcl-2 monoclo nal antibodies. In addition, Fas expression was quantitated by computerized cytometry. The results were compared by one-way analysis of variance follo wed by Bonferroni tests. In benign prostate samples, Bcl-2 and Fas were exp ressed on basal cells and secretory cells, respectively. Bcl-2 was not expr essed 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 me tastatic tumors (33%). Fas expression was significantly decreased (P < 0.00 1) in pi-estate cancer (0.20 pg/cell) compared with benign prostate (0.79 p g/cell). The decrease was inversely related to the malignant grade of the t umors (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 prost ate cancel. The decline begins in low-grade tumors. The lowest expression o ccurs in metastatic carcinomas, which are often Fas negative. Overexpressio n or Bcl-2 appears to be a later and unrelated molecular event. Both abnorm alities may be implicated in tumor progression by prolonging tumor cell sur vival. (C) 2000 Elsevier Science Inc. All rights reserved.