 |
|
Apoptosis Is Inhibited Early in the Dysplasia-Carcinoma Sequence of Barrett Esophagus
Natsuya Katada, MD;
Ronald A. Hinder, MD;
Thomas C. Smyrk, MD;
Naoki Hirabayashi, MD;
Galen Perdikis, MD;
Richard J. Lund, MD;
Timothy Woodward, MD;
Paul J. Klingler, MD
Arch Surg. 1997;132(7):728-733.
Abstract
| |
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 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
Author Affiliations
From the Department of Surgery, Creighton University (Drs Katada, Hirabayashi, Perdikis, and Lund), and Department of Pathology, Clarkson Hospital (Dr Smyrk), Omaha, Neb; and Department of Surgery, Mayo Clinic, Jacksonville, Fla (Drs Hinder, Woodward, and Klingler).
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Unlike Esophageal Squamous Cells, Barrett's Epithelial Cells Resist Apoptosis by Activating the Nuclear Factor-{kappa}B Pathway
Hormi-Carver et al.
Cancer Res. 2009;69:672-677.
ABSTRACT
| FULL TEXT
Biomarkers of Esophageal Adenocarcinoma and Barrett's Esophagus
McManus et al.
Cancer Res. 2004;64:1561-1569.
ABSTRACT
| FULL TEXT
Esophageal Cancer
Enzinger and Mayer
NEJM 2003;349:2241-2252.
FULL TEXT
Association of Metallothionein Expression and Lack of Apoptosis with Progression of Carcinogenesis in Barrett's Esophagus
Li et al.
Exp Biol Med 2003;228:286-292.
ABSTRACT
| FULL TEXT
Upregulation of the oncogene c-myc in Barrett's adenocarcinoma: induction of c-myc by acidified bile acid in vitro
Tselepis et al.
Gut 2003;52:174-180.
ABSTRACT
| FULL TEXT
Characterization and Isolation of Ductular Cells Coexpressing Neural Cell Adhesion Molecule and Bcl-2 from Primary Cholangiopathies and Ductal Plate Malformations
Fabris et al.
Am. J. Pathol. 2000;156:1599-1612.
ABSTRACT
| FULL TEXT
Molecular Evolution of the Metaplasia-Dysplasia-Adenocarcinoma Sequence in the Esophagus
Jankowski et al.
Am. J. Pathol. 1999;154:965-973.
ABSTRACT
| FULL TEXT
|
