Persistence of high-grade prostatic intra-epithelial neoplasia under combined androgen blockade therapy

The presence and morphology of high-grade prostatic intraepithelial neoplas ia (H-PIN) was blindly evaluated in 40 totally embedded radical prostatecto my specimens of patients with prostate cancer randomized to either a 3 (n = 18) or 6 months (n = 22) combined androgen blockade regimen before surgery . In 5 cases, neo-adjuvant therapy was abrogated some time before surgery I n the remaining cases, foci of H-PIN were identified in 72% and 59% of pros tates from patients treated for 3 and 6 months, respectively. Cellular feat ures used to distinguish H-PIN from normal glands were increased nuclear si ze, nuclear crowding, anisonucleosis, and disordered nuclear arrangement. I n some cases, density of cytoplasm was an additional feature. Unfortunately , the molecular marker erbB2 proved unhelpful for identification of H-PIN. The median number of prostatic glands involved by H-PIN was 19 +/- 21 (SD) glands in 3 months treated prostatectomies (n = 18) and 7 +/- 12 (SD) gland s in 6 months treated prostatectomies (n = 17), a nonsignificant difference (P = .17). H-PIN was localized within areas of residual carcinoma in 62% a nd 20%, respectively of prostatectomies of patients treated for 3 and 6 mon ths, respectively Architectural patterns of H-PIN differed at 3 and 6 month s of endocrine pretreatment: The predominant tufted pattern at 3 months was replaced by flat H-PIN at 6 months. The continued expression of androgen r eceptors and the cell cycle marker MIB-1 in persistent H-PIN suggests that recovery of androgen levels after cessation of androgen blockade therapy wi ll lead to its further expansion. Copyright (C) 1999 by W.B. Saunders Compa ny.