Nucleolar and AgNOR-analysis of Prostatic Intraepithelial Neoplasia (PIN), Atypical Adenomatous Hyperplasia (AAH) and Prostatic Carcinoma

Abstract

Atypical glandular proliferations of the prostate are found in combination with prostate carcinomas but also with benign prostatic hyperplasia (BPH). These atypical glandular lesions that mimic glandular carcinoma within the anterocentral part of the prostate (transition zone) are named "atypical adenomatous hyperplasia (AAH)." The term for atypical ductal and acinar mainly papillary and/or cribriform proliferations in the peripheral zone is "prostatic intraepithelial neoplasia (PIN)." In this study the significance of the status of nucleoli and the number of silver-stained nucleolar organizing regions (AgNOR) as a method for measuring proliferative activity was investigated in biopsies of AAH, PIN and carcinomas of different grades of malignancy. The aim was to prove whether there are relationships of AAH to low grade carcinomas on the one hand and of PIN to high grade carcinomas on the other hand. The frequency of nuclei with small nucleoli was low in BPH (0.6%). The values increased to 8.3% in AAH, and 28.7% in PIN. The frequency of nuclei with prominent nucleoli in low grade carcinomas was 41.7% and in high grade carcinomas 81.1%. Usually, one single nucleolus was found per nucleus. Multiple prominent nucleoli were found in high grade carcinomas and in some cases of high grade PIN only. The result of AgNOR-analysis was similar: low numbers in BPH, low to moderate values in AAH, moderate values in low grade carcinomas and high values in PIN, as well as high grade carcinomas. Besides correlation between topography, histology and cytology, the similarities of nucleolar and AgNOR-analysis between PIN and high grade carcinomas support the idea that PIN is the precursor of the peripheral prostatic carcinoma. The histological, cytological and cell kinetical features of AAH are intermediate between BPH and low grade carcinoma of the prostate. Therefore, the findings to date are inconclusive and further follow up studies are necessary to prove if AAH may be a precursor of transition zone carcinoma of the prostate.