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

Arch Surg. 1997 Jul;132(7):728-33. doi: 10.1001/archsurg.1997.01430310042007.


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 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.

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.

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Antibodies, Monoclonal
  • Apoptosis*
  • Barrett Esophagus / metabolism
  • Barrett Esophagus / pathology*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology*
  • Esophagitis, Peptic / metabolism
  • Esophagitis, Peptic / pathology*
  • Esophagus / anatomy & histology
  • Esophagus / metabolism
  • Esophagus / pathology*
  • Gene Expression Regulation*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunoenzyme Techniques
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Reference Values
  • Time Factors


  • Antibodies, Monoclonal
  • Proto-Oncogene Proteins c-bcl-2