ZONAL VARIATION OF APOPTOSIS AND PROLIFERATION IN THE NORMAL PROSTATEAND IN BENIGN PROSTATIC HYPERPLASIA

Objective To determine whether benign prostatic hyperplasia (BPH) resu lts from an imbalance between cell proliferation and apoptosis, and th e extent to which the rates of these opposing processes are altered wi th the expression of the anti-death oncoprotein bcl-2. Materials and m ethods Ten prostate glands from normal men (mean age 43.7 years) were sampled according to McNeal's zonal anatomy, in addition to 30 prostat e adenomas obtained from prostatectomy specimens from symptomatic pati ents (mean age 61.4 years). Tissue samples were fixed in formalin and embedded in paraffin. Proliferation and bcl-2 expression were assessed by immunostaining using Mib-1 and anti-bcl-2 antibodies, while apopto tic bodies were specifically stained using in situ nick translation. T he percentage of positive cells was determined by optical microscopy. Results In normal epithelium, the rates of proliferation and apoptosis were increased in the peripheral zone (Mib-1 1.7%, apoptotic bodies 3 .3%) compared with the central (0.2% vs 1.4%) and transition (0.1% vs 1.8%) zones. Proliferation was significantly greater in BPH than in no rmal prostate tissue (3.7%), contrasting with a stable rate of apoptos is (1.4%). In the normal prostate, bcl-2. was expressed by glandular a nd basal cells in the peripheral zone, In the central zone, bcl-2 was overexpressed in basal cells and in most glandular cells of the intral uminal ridges. Bcl-2 expression in the transition zone was limited to dispersed basal cells. In BPH, bcl-2 was strongly expressed by basal c ells in mature glandular formations and in most cells of young small n odules. Conclusion BPH may result from both an increase of proliferati on within the basal compartment and a failure of apoptosis to counterb alance basal cell proliferation. Increased expression of bcl-2 may par ticipate in this process by blocking apoptosis.