Genetic heterogeneity of surgically resected prostate carcinomas and theirbiopsy specimens is related to their histologic differentiation

BACKGROUND. In human prostate carcinogenesis, many genetic analyses includi ng conventional loss of heterozygosity (LOH) studies and microsatellite LOH analyses using the polymerase chain reaction method have revealed frequent LOH events at specific regions on chromosomes 3p, 7q, 8p, 10q, 16q, 17q, a nd 18q. METHODS. Using the laser-captured microdissection method, the authors extra cted genomic DNA from 23 cases of prostate carcinomas including 59 differen t lesions and 8 biopsy specimens. Using P-32-labeled primers, the authors a nalyzed six microsatellite loci (D3S647, D3S1228, D7S522, D8S137, NEFL, and D10S190) at which frequent LOH events have been reported. RESULTS. Of 10 cases In which the authors found LOH at any of the loci, 8 c ases showed a heterogeneous LOH pattern. In four cases, the authors also fo und replication error (RER) at some of the loci examined. There was no sign ificant relation between histologic differentiation and frequency of LOH or RER events. The overall LOH rate was found to be significantly lower in fo ci at classification pT2 (1 of 28 foci, 3%) compared with those at classifi cation pT3 (13 of 44 foci, 30%). Ln pT3 samples, LOH events in extraglandul ar foci (9 of 23 foci, 39%) tended to be more frequent compared with those in intraglandular foci (8 of 41 foci, 20%). The patterns of LOH events in b iopsy specimens correlated well with those in foci from surgical material s howing the same histologic characteristics. CONCLUSIONS. Prostate carcinoma is a genetically multicentric carcinoma, an d the genetic heterogeneity is well correlated with histologic differentiat ion. The frequency of LOH events increased according to the degree of tumor progression. (C) 2001 American Cancer Society.