The human prostate, a male sexual accessory tissue involved in seminal fluid production, has a remarkably high incidence of hyperplastic and neoplastic disease. The present study was carried out on one hundred and twenty (120) specimens divided into two groups; group 1: Included forty cases of benign prostatic hyperplasia (BPH) and group 2: Included sixty cases of prostatic adenocarcinoma (PC) (22 were low grade; GS: 2-6 and 38 were high grade; GS: 7- 10),in addition to twenty cases of histologically normal prostates taken as controls. Immunohistochemical technique was applied to detect Bcl-2 as well as ER α positivity in all specimens. Group 1 showed the following profile: ER α (+) in all cases (100%), Bcl-2 (-) in 95%, ERα (+) / Bcl-2 (+) in 95%, ERα (-) / Bcl-2 (+) in 0%, ERα (+) / Bcl-2 (-) in 5% and ERα (-) / Bcl-2 (-) in 0% of cases while group 2 showed the following profile: ERα (+) in 30%, Bcl-2 (+) in 21.7%, ERα (+) / Bcl-2 (+) in 15%, ERα (-) / Bcl-2 (+) in 6.7%, ERα (+) / Bcl-2 (-) in 15% and ERα (-) / Bcl-2 (-) in 70% of cases. The mean epithelial ER α -immunolabeling was, however, significantly increased in group 2 than in group 1 (P < 0.05) which, in turn, being higher than the normal cases (P<0.05 ) . Among group 2 , the mean ER α
was significantly more in high grade than in low grade tumors (P < 0.05), however, the mean ER α immunolabeling revealed no significant correlation with T-stage (P = 0.219) or with the clinical stage (P = 0.391). In contrast, the Bcl-2 immunostaining was statistically higher in group 1 than in group 2 (P < 0.05) and showed a significant correlation with T stage (P < 0.05) although the study displayed no significant correlation between Bcl-2 immunopositivity and either Gleason score (P = 0.125) or the histologic grade (P = 0.146). In addition, combined ER α (+)/ Bcl 2 (+) immunoreactivity demonstrated the aggressive subgroup of PC cases more accurately than either ER α (+) or Bcl-2 (+) alone. Finally, multivariate analysis showed that the Bcl-2, proved to be an independent prognostic indicator (P < 0.05). Thus, the immunohistochemical expression of ER α and Bcl-2 protein in prostatic tissue may aid in better understanding the biology and genesis of both prostatic hyperplasia and carcinoma .