GENETIC INSTABILITY OF MICROSATELLITES IN ENDOMETRIAL CARCINOMA

Hereditary nonpolyposis colorectal cancer (HNPCC) is characterized by a familial predisposition to colorectal carcinoma and extracolonic can cers of the gastrointestinal, urological, and female reproductive trac ts, notably the endometrium. A genetic locus for HPNCC was recently de termined by linkage analysis to exist on chromosome 2p; both sporadic and HNPCC-associated colorectal carcinomas exhibit a ''replication err or'' phenotype, characterized by instability of dinucleotide repeat se quences throughout the genome. Here, we address the hypothesis that th e replication error phenotype would be evident in some fraction of spo radic endometrial carcinomas or in those associated with HNPCC. Micros atellite instability was observed in 17% of sporadic endometrial carci nomas and in 75% of those tumors associated with HNPCC. These data ind icate that the HNPCC gene is also involved in heritable and somatic fo rms of endometrial carcinoma.