RER plus phenotype in prostate intra-epithelial neoplasia associated with human prostate-carcinoma development

The mutator (RER+) phenotype has been shown to be a mutational mechanism fo r tumour-suppressor-gene inactivation in colorectal cancer. A group of 60 p rostate-carcinoma patients was studied to determine the frequency, intratum our distribution and timing of mutator phenotype in this cancer. Ten micros atellite loci were analyzed in 172 carcinoma foci (CF) and in 57 associated non-cancerous prostate tissues, including 31 areas of prostate intra-epith elial neoplasia (PIN) and 26 non-dysplastic areas with glandular hyperplasi a (HP), We detected lesions with the RER+ phenotype in 42% (25/60) of the p rostate tumours. Clonal foci with RER+ phenotype were detected at similar f requencies in precancereous PIN (16%, 5/31) as in associated carcinoma foci (22%, 37/172), but were detected in only one of the 26 non-dysplastic pros tate tissues studied (4%). Thus, clonal RER+ foci were significantly more f requent in CF than in HP (p < 0.05). MI itself was significantly more frequ ent in CF (53%, p < 0.0001) and in PIN (35%, p < 0.05) than in HP (12%). Fu rthermore, 5 PIN harboured microsatellite mutations also detected in the as sociated cancer. Our overall results therefore strongly suggest that the mu tator phenotype may occur as an early event in prostate tumorigenesis. Int. J. Cancer 82:635-639, 1999. (C) 1999 Wiley-Liss, Inc.