THE RELATIONSHIP BETWEEN ANEUPLOIDY AND THE DEVELOPMENT OF HIGH GRADE DYSPLASIA IN PATIENTS WITH BARRETT'S ESOPHAGUS. D.._LL. Limauro, S. Shackney, M.A. Jones, A.A. Pollice, C.A. Smith, R.M. Agrawal, GJ. Brodmerkel, Jr., Division of Gastroenterology, and the Laboratory of Cancer Cell Biology and Genetics, Allegheny Cancer Center, Allegheny General Hospital, The Medical College of Pennsylvania and Hahnemann University, Pittsburgh, PA Methods: We report on 29 patients with Barrett's Esophagus who were followed between 3/87 and 11/95, who initially had histologically-documented specialized columnar metaplasia and no evidence of adenocarcinoma, and had at least two sequential DNA analyses by flow cytometry (FCM) on biopsy, material with at least I0,000 cells analyzed per sample. Results: Median length of follow-up from time of first FCM to 11/1/95 was 66 months (range 2-114 months). Among 24 patients who were diploid and remained diploid, none developed high-grade dysplasia or adenocarcinoma (median fellow-up 68 months; range 22-108 months). Five of 29 patients (17%) developed aneuploidy during the course of follow-up (median follow-up 40 months; range 2-97 months). In 3 of these 5 (60%), high grade dysplasia or adenocarcmoma developed concomitantly with, or after, the development of aueuploidy. I , 2 of the 5 patients, high grade dysplasia preceded the development of aneuploidy by 2 and 9 months, respectively. Among 26 patients who were seen iuitially with intestinal metaptasia and did not develop high-grade dysplasia or adenocarcinoma, 24 (92%) remained diploid. Two of 26 palicnts developed aneuploidy at intervals of 30 months and 73 months after initial diploidy by FCM. One patient who developed aneuploidy at 73 months also developed low-grade dysplasia concurrently with aneuploidy by FCM. Conclusions: I) Most patients with Barrett's Esophagus have an indolent coarse, developing neither aneuploidy nor high-grade dysplasia ever a median follow-up of 5-1/2 years. 2) The development of high grade dysplasia is invariably associated with the development of aneuploidy by FCM. We hypothesize thin patients with aneuploidy and intestinal metaplasia only are at increased risk for progressioa to high-grade dysplasia in the future, 3) The development of aseuploidy often precedes the development of high-grade dysplasia, but the two may dcvclap simultaneously, or aneuploidy may follow the development of high grade dysplasia. Additional genetic markers may be useful in detecting the accumulation of genetic abnormalities that are associated with minor progression.