High grade prostatic intraepithelial neoplasia. The most likely precursor of prostate cancer

Abstract

The search for the precursor of prostatic adenocarcinoma has focused in recent years on the spectrum of histopathologic changes referred to as high grade prostatic intraepithelial neoplasia (PIN). This review describes the diagnostic criteria and clinical significance of PIN. PIN coexists with cancer in more than 85% of cases, but retains an intact or fragmented basal cell layer, unlike cancer, which lacks a basal cell layer. High grade PIN in biopsies predicts the presence of cancer in subsequent biopsies, and PIN provides the highest risk ratio of all known predictive factors (14.93). The continuum that culminates in high grade PIN and early invasive cancer is characterized by progressive basal cell layer disruption, loss of markers of secretory differentiation, nuclear and nucleolar abnormalities, increasing proliferative potential, 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 thirties. The significance of recognizing PIN is based on its strong association with prostatic carcinoma. This finding indicates the need for repeat biopsy and follow-up when PIN is identified on biopsy, especially in patients with elevated serum prostate specific antigen concentration. PIN also offers promise as an intermediate end point in studies of chemoprevention of prostatic carcinoma. Cancer 1995 ;75 :1823-36.