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

The presence and morphology of high-grade prostatic intraepithelial neoplasia (H-PIN) was blindly evaluated in 40 totally embedded radical prostatectomy 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. In the remaining cases, foci of H-PIN were identified in 72% and 59% of prostates from patients treated for 3 and 6 months, respectively. Cellular features used to distinguish H-PIN from normal glands were increased nuclear size, nuclear crowding, anisonucleosis, and disordered nuclear arrangement. In 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) glands in 6 months treated prostatectomies (n = 17), a nonsignificant difference (P = .17). H-PIN was localized within areas of residual carcinoma in 62% and 20%, respectively of prostatectomies of patients treated for 3 and 6 months, respectively. Architectural patterns of H-PIN differed at 3 and 6 months of endocrine pretreatment: The predominant tufted pattern at 3 months was replaced by flat H-PIN at 6 months. The continued expression of androgen receptors and the cell cycle marker MIB-1 in persistent H-PIN suggests that recovery of androgen levels after cessation of androgen blockade therapy will lead to its further expansion.