Prospective origins of prostate carcinoma. Prostatic intraepithelial neoplasia and atypical adenomatous hyperplasia

Abstract

Background: The search for the precursor of prostatic adenocarcinoma has focused in recent years on two histopathologic findings: high grade prostatic intraepithelial neoplasia (PIN) and atypical adenomatous hyperplasia (AAH). This article describes the diagnostic criteria and clinical significance of PIN and AAH.

Methods and results: PIN is the most likely precursor of prostate carcinoma. The continuum that culminates in high grade PIN and early invasive carcinoma is characterized by progressive basal cell layer disruption, loss of markers of secretory differentiation, nuclear and nucleolar abnormalities, increasing proliferative potential, increasing microvessel density, variation in DNA content, and allelic loss. Clinical studies suggest that PIN predates carcinoma by 10 years or more, with low grade PIN first appearing in men in their 30s. AAH is usually found in the transition zone, and shows a weak and inconclusive link to well differentiated adenocarcinoma of the transition zone.

Conclusions: The significance of recognizing PIN is based on its strong association with prostatic carcinoma. PIN coexists with carcinoma in most cases, but retains an intact or fragmented basal cell layer, unlike carcinoma, which lacks a basal cell layer. High grade PIN in biopsies predicts the presence of carcinoma in subsequent biopsies, and PIN provides the highest risk ratio of all known predictive factors. This finding indicates the need for repeat biopsy and follow-up when PIN is identified in a biopsy, especially in patients with an elevated serum prostate specific antigen concentration. PIN also offers promise as an intermediate endpoint in studies of chemoprevention of prostatic carcinoma. Unlike PIN, AAH is weakly linked to carcinoma, and current data indicate that no follow-up is necessary for patients with this finding.