CLINICAL AND PATHOLOGICAL SIGNIFICANCE OF MICROSATELLITE INSTABILITY IN SPORADIC ENDOMETRIAL CARCINOMA

Defective DNA mismatch repair in neoplasia is manifested by extra, abe rrant bands within multiple microsatellite markers. The replication er ror (RER) phenotype is present in most colorectal and endometrial carc inomas ill patients with the hereditary nonpolyposis colorectal carcin oma syndrome. In addition, a minority of sporadic colorectal and endom etrial carcinomas are RER positive. RER in sporadic colorectal carcino mas has been associated with improved prognosis, but its clinical sign ificance in sporadic endometrial cancer has not been characterized. We analyzed DNA extracted from 109 formalin-fixed sporadic endometrial c arcinomas for microsatellite instability. The RER-positive phenotype w as demonstrated by microsatellite instability in more than one of the eight dinucleotide markers tested, RER was correlated with pathologica l and clinical parameters as well as with immunohistochemical staining for the p53 gene product and alterations in codon 12 of Ki-ras Nine p ercent of the endometrial carcinomas were RER positive, and RER was si gnificantly associated with high grade and adverse outcome. We found n o significant correlation of RER with histological subtype, stage, dep th of invasion, mutations in the 12th codon of Ki-ras, or p53 immunore activity. We conclude that the RER phenotype is present ill a minority Of sporadic endometrial carcinomas and is associated with high grade and poor prognosis.