To evaluate the alteration of apoptosis in the esophageal epithelium during the esophagitis–Barrett esophagus–adenocarcinoma sequence.
Archival tissue samples of 85 lesions in 58 cases were used. The lesions represented 7 groups: normal esophagus (n=10), reflux esophagitis (n=12), Barrett metaplasia (n=21), Barrett low-grade dysplasia (n=17), Barrett high-grade dysplasia (n=5), well- or moderately differentiated adenocarcinoma (n=10), and poorly differentiated adenocarcinoma (n=10). Apoptotic cells with fragmented DNA were detected by the terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate (dUTP)–biotin nick end labeling (TUNEL) method. Monoclonal antibodies against bcl-2 protein were applied using the avidin-biotin complex immunoperoxidase method.
The esophagitis group showed many apoptotic cells on the epithelial surface; in the other groups, few apoptotic cells were seen. Weak bcl-2 expression was seen in the basal cells in normal subjects and those with esophagitis. There was overexpression of bcl-2 in 72% of Barrett metaplasia, 100% of Barrett low-grade dysplasia, 25% of Barrett high-grade dysplasia, 40% of well- or moderately differentiated adenocarcinoma, and 20% of poorly differentiated adenocarcinoma.
Increased apoptosis in reflux esophagitis may be a protective mechanism counteracting increased proliferation. Inhibition of apoptosis by overexpression of bcl-2 protein occurs early in the dysplasiacarcinoma sequence of Barrett esophagus. The resulting 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 cells acquire other ways of avoiding apoptosis as malignancy appears.Arch Surg. 1997;132:728-733
Katada N, Hinder RA, Smyrk TC, Hirabayashi N, Perdikis G, Lund RJ, Woodward T, Klingler PJ. Apoptosis Is Inhibited Early in the Dysplasia-Carcinoma Sequence of Barrett Esophagus. Arch Surg. 1997;132(7):728-733. doi:10.1001/archsurg.1997.01430310042007