Apoptosis is inhibited early in the dysplasia-carcinoma sequence of Barrett esophagus

Natsuya Katada, Ronald A. Hinder, Thomas C. Smyrk, Naoki Hirabayashi, Galen Perdikis, Richard J. Lund, Timothy Woodward, Paul J. Klingler

Research output: Contribution to journalArticlepeer-review

87 Scopus citations


Objective: To evaluate the alteration of apoptosis in the esophageal epithelium during the esophagitis-Barrett esophagus-adenocarcinoma sequence. Design: 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 deoxy- nucleotidyl 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. Results: 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. Conclusions: 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 dysplasia- carcinoma 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.

Original languageEnglish (US)
Pages (from-to)728-733
Number of pages6
JournalArchives of Surgery
Issue number7
StatePublished - 1997

ASJC Scopus subject areas

  • Surgery


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