THE MOLECULAR BASIS FOR CARCINOGENESIS IN METAPLASTIC COLUMNAR-LINED ESOPHAGUS

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BARRETT'S ESOPHAGUS

Barrett's esophagus is an acquired condition in which the normal squamous epithelium of the esophagus is replaced by a metaplastic columnar lining.85, 86 This change is strongly associated with chronic gastroesophageal reflux.34, 101 Barrett's esophagus predisposes to malignancy, being associated with a risk of primary esophageal adenocarcinoma up to 125-fold higher than that in the general population.36, 66, 100 This type of cancer is one of the most rapidly increasing carcinomas in Western

HEREDITARY AND ENVIRONMENTAL FACTORS IN BARRETT'S ESOPHAGUS

Barrett's metaplasia is generally believed to represent an acquired response to chronic gastroesophageal reflux. The great majority of patients with gastroesophageal reflux, however, do not develop Barrett's esophagus. Therefore, other factors are assumed to contribute to the pathogenesis of Barrett's metaplasia. These factors are presently unknown. In this context, families containing multiple members with Barrett's esophagus have now been reported.51 To identify a chromosomal locus and a gene

BIOLOGY OF BARRETT'S ESOPHAGUS AND ADENOCARCINOMA

Essential to the discussion of Barrett's esophagus–associated carcinogenesis is the concept of metaplasia. Metaplasia is defined as the conversion of one differentiated cell type to another, with the second type being one that is not normally present in the involved organ. Metaplasia usually occurs in the setting of persistent injury or inflammation. In general, metaplastic epithelia appear to be predisposed to neoplastic transformation.17, 35, 56, 63, 95 The presence of specialized intestinal

SUMMARY

A wide variety of biologic events and mechanisms appear to have roles in the development and progression of Barrett's esophagus–associated neoplastic lesions. Figure 5 is a schematic depiction of these events. This is known as an infernogram (named after Dante's Inferno) (S. Kern, unpublished presentations, 1996). Events at the bottom rings of the inferno are high-frequency mutations; nearer to the top of the inferno are the less common events. The next several years promise many further

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    Address reprint requests to Stephen J. Meltzer, MD, Division of Gastroenterology, University of Maryland Hospital, 22 S. Greene Street, Room #N3W62, Baltimore, MD 21201

    *

    From the Department of Medicine, Division of Gastroenterology, University of Maryland Medical School, Baltimore, Maryland

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    Copyright © 1997 W. B. Saunders Company. Published by Elsevier Inc. All rights reserved.