RESISTANCE TO APOPTOSIS AND UP-REGULATION OF BCL-2 IN BENIGN PROSTATIC HYPERPLASIA AFTER ANDROGEN DEPRIVATION

Purpose: Benign prostatic hyperplasia (BPH) is related to advancing ag e and the presence of androgens and occurs in virtually all older men. BPH causes morbidity, most often by urinary obstruction, in a substan tial fraction of men over sixty. Both finasteride and androgen ablatio n induce partial diminution in BPH that occurs over weeks to months. T his is in contrast to the often rapid involution seen in both normal p rostatic epithelium and prostatic carcinoma in response to androgen wi thdrawal. This study was performed to analyze the response of prostati c cells, and in particular BPH, to acute androgen ablation. Materials and Methods: We subjected a cohort of 26 men to androgen ablation with goserelin, a gonadotrophin releasing hormone agonist, for 3-4 weeks p rior to radical prostatectomy for prostate cancer. Preablation biopsy specimens and prostatectomy specimens were immunohistochemically stain ed for apoptotic cells and for expression of apoptosis regulatory prot eins Bcl-2, Bax, Bcl-x, and Bak. Results: Normal prostatic epithelial cells and prostate cancer responded to hormone deprivation by undergoi ng apoptosis, but in 19/26 specimens prostatic hyperplasia had a total absence of apoptosis. In all 26 specimens, benign prostatic hyperplas ia demonstrated increased expression of the Bcl-2 protein, but no chan ge in the expression of Bax, Bcl-x, and Bak. In contrast, adjacent nor mal and malignant prostatic epithelium showed positive staining for ap optosis and did not alter Bcl-2 expression in response to androgen abl ation. Conclusions: BPH demonstrated increased staining for Bcl-2 afte r androgen deprivation that; may render hyperplastic epithelium relati vely resistant to apoptosis induced acutely by androgen withdrawal.