APOPTOSIS IS INHIBITED EARLY IN THE DYSPLASIA-CARCINOMA SEQUENCE OF BARRETT-ESOPHAGUS

Objective: To evaluate the alteration of apoptosis in the esophageal e pithelium during the esophagitis-Barrett esophagus-adenocarcinoma sequ ence. Design: Archival tissue samples of 85 lesions in 58 cases were u sed. The lesions represented 7 groups: normal esophagus (n=10), reflux esophagitis (n=12), Barrett metaplasia (n=21),Barrett low-grade dyspl asia (n=17), Barrett high-grade dysplasia (n=5), well- or moderately d ifferentiated adenocarcinoma (n=10), and poorly differentiated adenoca rcinoma (n=10). Apoptotic cells with fragmented DNA were detected by t he terminal deoxynucleotidyl transferase-mediated deoxyuridine triphos phate (dUTP)-biotin nick end labeling (TUNEL) method. Monoclonal antib odies against bcl-2 protein were applied using the avidin-biotin compl ex immunoperoxidase method. Results: The esophagitis group showed many apoptotic cells on the epithelial surface; in the other groups, few a poptotic cells were seen. Weak bcl-2 expression was seen in the basal cells in normal subjects and those with esophagitis. There was overexp ression of bcl-2 in 72% of Barrett metaplasia, 100% of Barrett low-gra de dysplasia, 25% of Barrett high-grade dysplasia, 40% of well- or mod erately differentiated adenocarcinoma, and 20% of poorly differentiate d adenocarcinoma. Conclusions: Increased apoptosis in reflux esophagit is may be a protective mechanism counteracting increased proliferation . Inhibition of apoptosis by overexpression of bcl-2 protein occurs ea rly in the dysplasia-carcinoma sequence of Barrett esophagus. The resu lting prolongation of cell survival may promote neoplastic progression . Despite the absence of apoptosis, bcl-2 was not widely overexpressed in Barrett high-grade dysplasia and adenocarcinoma, suggesting that c ells acquire other ways of avoiding apoptosis as malignancy appears.