Molecular evidence supporting the precursor nature of atypical adenomatous hyperplasia of the prostate

Abstract Atypical adenomatous hyperplasia (AAH) of the prostate is characterized by lobular proliferation of closely packed small acini. It is hypothesized that AAH is a precursor lesion for low‐grade prostate cancer arising from the transition zone. Telomere dysfunction is common during malignant transformation of epithelia. In this study, we investigate telomere shortening in AAH ( n = 93), high‐grade prostatic intraepithelial neoplasia (HGPIN) ( n = 68), and prostatic adenocarcinoma (PCA) ( n = 70) using quantitative fluorescence in situ hybridization. Twenty percent (19 of 93) of AAH specimens, 68% (46 of 68) of HGPIN, and 83% (58 of 70) of PCA showed significant telomere shortening. Thirty‐two percent of AAH lesions had α‐methylacyl‐CoA racemase (AMACR) expression, a sensitive and specific marker for HGPIN and PCA. AMACR expression in AAH was seen more frequently in AAH foci with telomere shortening or coexisting PCA. Our findings indicate that a subset of AAH lesions have telomere shortening and AMACR expression, suggesting that these foci may be precursors for PCA.