MICROSATELLITE INSTABILITY OCCURS FREQUENTLY AND IN BOTH DIPLOID AND ANEUPLOID CELL-POPULATIONS OF BARRETTS-ASSOCIATED ESOPHAGEAL ADENOCARCINOMAS

Alterations of microsatellites consisting of extra or missing copies o f these sequences occur at relatively high frequencies in sporadic and hereditary colorectal adenocarcinomas, gastric and pancreatic cancers , and at fewer frequencies in endometrial, bladder, ovarian, and other carcinomas. We determined the prevalence of microsatellite instabilit y in esophageal adenocarcinoma, Barrett's esophagus, and squamous cell carcinoma of the esophagus. Assays were performed on 105 patients, in cluding 28 subjects with Barrett's metaplasia, 36 with Barrett's-assoc iated adenocarcinoma, and 42 with primary esophageal squamous cell car cinoma. Flow cytometric nuclear sorting based on DNA content was perfo rmed on 25 of the adenocarcinomas prior to DNA extraction. Specimens f rom 11 of the 106 patients (10%) showed instability at 1 or more chrom osomal loci. Instability was seen in 2 of 28 patients (7%) with Barret t's metaplasia alone, in 8 of 36 (22%) with adenocarcinoma, and in 1 o f 42 (2%) with squamous cell carcinoma. Among the 25 flow cytometrical ly sorted adenocarcinomas, instability occurred in 8 (32%); sorted dip loid nuclei from these tumors showed instability in 4 of 8 cases (50%) . These data indicate that microsatellite instability occurs frequentl y in Barrett's-associated esophageal adenocarcinoma. They also suggest that in esophageal adenocarcinomas, microsatellite instability can de velop as an early event in metaplasia and in diploid tumor cells, befo re aneuploidy occurs.