Effect of androgen deprivation therapy on prostatic intraepithelial neoplasia

There is a marked decrease in the prevalence and extent of high-grade prost atic intraepithelial neoplasia (PIN) in men with prostate cancer after andr ogen deprivation therapy (ADT) when compared with untreated cases. Basal ce ll hyperplasia, cytoplasmic clearing, and prominent atrophy of benign acini , with decreased ratio of acini to stroma, accompany this decrease. These f indings indicate that the benign and dysplastic prostatic epithelium is and rogen dependent. In the normal prostatic epithelium, luminal secretory cell s are more sensitive to the absence of androgen than basal cells, and the p roliferative cells of high-grade PIN share this androgen sensitivity. The l oss of some normal, hyperplastic, and dysplastic epithelial cells with ADT is probably because of acceleration of programmed single-cell death. Remark ably little is known about the comparative effect of different forms of che mical ADT on PIN and cancer, although there appears to be a limited and con sistent repertoire of morphologic responses to all forms of this therapy. C onversely, blockade of 5 alpha -reductase with finasteride has little or no effect on PIN (or benign epithelium and cancer), unlike other forms of ADT . A recent international consensus conference sponsored by the World Health Organization concluded that identification of high-grade PIN offered the p ossibility of chemoprevention with hormonal therapy to block the developmen t of clinical cancer. Multiple chemoprevention trials are planned or under way to address this hypothesis. (C) 2001, Elsevier Science Inc.