BARRETTS-ESOPHAGUS - MICROSATELLITE ANALYSIS PROVIDES EVIDENCE TO SUPPORT THE PROPOSED METAPLASIA-DYSPLASIA-CARCINOMA SEQUENCE

The development of adenocarcinoma in Barrett's oesophagus is proposed to occur via a stepwise progression recognised histologically as a met aplasia-dysplasia-carcinoma sequence. In order to identify chromosomal loci involved in the malignant transformation of Barrett's epithelium and the development of oesophageal adenocarcinoma, microsatellite ana lysis was carried out on 17 cases of Barrett's-associated oesophageal adenocarcinoma. Samples of premalignant Barrett's epithelium adjacent to adenocarcinoma were obtained from seven of these cases. Allelic imb alance was detected in >45% of informative cases of oesophageal adenoc arcinoma on chromosome arms 3q (65%), 4q (71%), 5q (59%), 6q (59%), 9p (50%), 9q (47%), 12p (47%), 12q (65%), 17p (76%), and 18q (75%). Alle lic imbalance at 4q, 17p, and 18q was significantly higher than the up per 95% confidence interval for background allelic imbalance. Allelic imbalance was detected at several loci in the premalignant epithelium from five of the seven cases studied. These loci included several chro mosomal arms that had demonstrated high levels of allelic imbalance in oesophageal adenocarcinoma, namely, 4q (one case), 5q (two cases), 9 (three cases), 12q (five cases), 17p (four cases), and 18q (two cases) , Novel microsatellite alleles were detected in both premalignant and malignant Barrett's epithelium. In three cases, dysplastic Barrett's e pithelium and adjacent adenocarcinoma demonstrated the same pattern of novel microsatellite alleles at a number of loci, In conclusion, thes e data indicate chromosomal loci which may be specifically involved in the histological progression of Barrett's epithelium. The detection o f shared novel microsatellite alleles in premalignant and malignant Ba rrett's epithelium is consistent with a process of clonal expansion un derlying this progression. (C) 1998 Wiley-Liss, Inc.