Prostatic intraepithelial neoplasia: an update.

High-grade prostatic intraepithelial neoplasia (HGPIN) is commonly encountered on prostate needle biopsies and, based on epidemiologic, molecular, and animal models, has proven to be the most significant risk factor for prostate cancer and likely represents the premalignant phase of prostatic adenocarcinoma. This lesion is characterized by cellular proliferations within pre-existing ducts and glands, with nuclear and nucleolar enlargement similar to prostate cancer. However, unlike cancer, HGPIN retains a basal cell layer identifiable by immunohistochemistry with the basal cell-specific antibody cytokeratin 34bE12. The incidence of HGPIN identified in needle biopsies is as high as 25%, increases with age, and coexists with prostate cancer in approximately 85% of cases. There appears to be no causal relationship between HGPIN and serum prostate-specific antigen (total, percent free, or density) or radiographic characteristics on transrectal ultrasound. In a large series, the identification of HGPIN on initial needle biopsy is associated with about a 35% risk of prostate cancer on subsequent biopsies. Thus, the finding of HGPIN on prostate needle biopsy necessitates a second biopsy in a patient eligible for curative treatment. As a precursor lesion, HGPIN is currently a target for chemopreventive strategies, including antiandrogens and nutritional supplementation.