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Microsatellite Instability Occurs Frequently and in Both Diploid and Aneuploid Cell Populations of Barrett's-associated Esophageal Adenocarcinomas¹

Department of Medicine, Gastroenterology Division [S. J. M., J. Y., B. M., M-G. R., J. L. R., J. M. A.], and Departments of Surgery [M. J. K.] and Pathology [J. C., E. H.], Veterans Affairs and University of Maryland Hospitals, Baltimore, Maryland 21201, and Department of Medicine, Gastroenterology Division, University of Washington, Seattle, Washington 98195 [B. J. R.]

Alterations of microsatellites consisting of extra or missing copies of these sequences occur at relatively high frequencies in sporadic and hereditary colorectal adenocarcinomas, gastric and pancreatic cancers, and at lower frequencies in endometrial, bladder, ovarian, and other carcinomas. We determined the prevalence of microsatellite instability in esophageal adenocarcinoma, Barrett's esophagus, and squamous cell carcinoma of the esophagus. Assays were performed on 105 patients, including 28 subjects with Barrett's metaplasia, 36 with Barrett's-associated adenocarcinoma, and 42 with primary esophageal squamous cell carcinoma. Flow cytometric nuclear sorting based on DNA content was performed on 25 of the adenocarcinomas prior to DNA extraction. Specimens from 11 of the 106 patients (10%) showed instability at 1 or more chromosomal loci. Instability was seen in 2 of 28 patients (7%) with Barrett's metaplasia alone, in 8 of 36 (22%) with adenocarcinoma, and in 1 of 42 (2%) with squamous cell carcinoma. Among the 25 flow cytometrically sorted adenocarcinomas, instability occurred in 8 (32%); sorted diploid nuclei from these tumors showed instability in 4 of 8 cases (50%). These data indicate that microsatellite instability occurs frequently in Barrett's-associated esophageal adenocarcinoma. They also suggest that in esophageal adenocarcinomas, microsatellite instability can develop as an early event in metaplasia and in diploid tumor cells, before aneuploidy occurs.

¹ Supported by American Cancer Society Grants EDT-74525 and EDT-21E, NIH Grant R01 CA55814, and the Office of Medical Research, Department of Veterans Affairs.

² To whom requests for reprints should be addressed, at University of Maryland N3W62, 22 S. Greene Street, Baltimore, MD 21201.

Received 4/ 1/94. Accepted 5/18/94.

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