Histological markers of risk and the role of high-grade prostatic intraepithelial neoplasia

Abstract

The marked discrepancy between the prevalence of preclinical prostate cancer and the incidence of clinically manifest disease indicates a long latency phase and significant heterogeneity in the progression potential of early neoplastic lesions. There are a variety of histologic changes within prostatic epithelium that have been termed atypical or dysplastic. The 2 most widely studied of these lesions are prostatic intraepithelial neoplasia (PIN) and atypical adenomatous hyperplasia (AAH). Although associations between AAH and adenocarcinoma are spurious, those linking high-grade PIN (HGPIN) to cancer are far more established. There is a significantly increased risk for patients with isolated HGPIN to have prostate cancer confirmed on subsequent biopsy, suggesting that HGPIN is a marker for prostate carcinoma in addition to its potential role as a premalignant lesion. Autopsy studies reveal that HGPIN is found in association with cancer in 63% to 94% of malignant and 25% to 43% of benign prostates. Data on age and race reveal that African American men develop more extensive HGPIN at a younger age than white men. A wide spectrum of molecular/genetic abnormalities appears to be common to both HGPIN and prostate cancer. Data loss of 8p, 10q, 16q, 18q, and gain of 7q31, 8q, multiple copies of the c- myc genes, along with changes in chromatin texture, telomerase activity, cell cycle status, and proliferative indices collectively suggest that HGPIN is intermediate between benign epithelium and prostatic carcinoma with respect to these markers. These data indicate that HGPIN is important in neoplastic progression, and may present an appropriate target/marker for chemoprevention.