MICROSATELLITE INSTABILITY IN ADENOCARCINOMA OF THE PROSTATE

Instability of dinucleotide tandem repeat sequences has been reported to play a major role in the carcinogenic pathway of familial colon can cer, as well as a potential rob in the carcinogenesis of other sporadi c neoplasms. To determine the frequency of short tandem repeat instabi lity in adenocarcinoma of the prostate, we studied 40 tumors that were stratified according to tumor grade. The tissue samples were screened with di-, tri- and tetranucelotide markers spanning a wide range of c hromosomal loci, including an androgen receptor gene trinucleotide rep eat, Microsatellite instability was observed overall in only one of th e 40 (2.5%) prostate adenocarcinomas studied, This replication error-p ositive tumor demonstrated repeat length alterations at two loci. Five other tumors showed an alteration in microsatellite size at a single locus. These tumors were not considered to have the microsatellite ins tability phenotype. All changes were identified either within tetranuc leotide sequences or within the androgen receptor gene repeat (4 of 20 total markers analyzed). Both repeat length expansions and contractio ns were identified The replication error-positive case also included s eparate metastatic nodal tissue Additional microsatellite analysis of the metastatic tumor tissue revealed allelic patterns identical with t he normal tissue control Our data indicate that microsatellite instabi lity is rare in prostate adenocarcinoma. Therefore, observation of thi s low replication error frequency suggests that most prostate carcinom as develop in the absence of widespread accumulation of somatic mutati ons in short tandem repeat sequences, Additionally, these genetic alte rations appear to occur more often in tetranucleotide repeat sequences as well as in an androgen receptor gene trinucleotide repeat.