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From the Institute for Cancer Studies,*
University of
Birmingham, Birmingham, United Kingdom; the Histopathology
Unit,
Imperial Cancer Research Fund, London,
United Kingdom; the Gastroenterology
Division,
Department of Medicine, VA Maryland
Health System, University of Maryland, Baltimore, Maryland; the
Gastrointestinal Section,§
Palo Alto Veterans
Affairs Health Care System, Palo Alto, California; the Department of
Pathology,¶ Leuven University, Leuven,
Belgium; and the Division of Thoracic Surgery,||
Dalhousie
University, Halifax, Nova Scotia, Canada
The incidence of adenocarcinoma of the esophagus has been increasing in developing countries over the last three decades and probably reflects a genuine increase in the incidence of its recognized precursor lesion, Barrett's metaplasia. Despite advances in multimodality therapy, the prognosis for invasive esophageal adenocarcinoma is poor. An improved understanding of the molecular biology of this disease may allow improved diagnosis, therapy, and prognosis. We focus on recent developments in the molecular and cell biology of Barrett's metaplasia, a heterogeneous lesion affecting the transitional zone of the gastro-esophageal junction whose associated molecular alterations may vary both in nature and temporally. Early premalignant clones produce biological and genetic heterogeneity as seen by multiple p53 mutations, p16 mutations, aneuploidy, and abnormal methylation resulting in stepwise changes in differentiation, proliferation, and apoptosis, allowing disease progression under selective pressure. Abnormalities in expression of growth factors of the epidermal growth factor family and cell adhesion molecules, especially cadherin/catenin complexes, may occur early in invasion. Exploitation of these molecular events may lead to a more appropriate diagnosis and understanding of these lesions in the future.
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M. J. Roth, N. Hu, M. R. Emmert-Buck, Q.-H. Wang, S. M. Dawsey, G. Li, W.-J. Guo, Y.-Z. Zhang, and P. R. Taylor Genetic Progression and Heterogeneity Associated with the Development of Esophageal Squamous Cell Carcinoma Cancer Res., May 1, 2001; 61(10): 4098 - 4104. [Abstract] [Full Text]
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C. A. Eads, R. V. Lord, K. Wickramasinghe, T. I. Long, S. K. Kurumboor, L. Bernstein, J. H. Peters, S. R. DeMeester, T. R. DeMeester, K. A. Skinner, et al. Epigenetic Patterns in the Progression of Esophageal Adenocarcinoma Cancer Res., April 1, 2001; 61(8): 3410 - 3418. [Abstract] [Full Text]
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 P. Taniere, G. Martel-Planche, D. Maurici, C. Lombard-Bohas, J.-Y. Scoazec, R. Montesano, F. Berger, and P. Hainaut Molecular and Clinical Differences between Adenocarcinomas of the Esophagus and of the Gastric Cardia Am. J. Pathol., January 1, 2001; 158(1): 33 - 40. [Abstract] [Full Text] [PDF]
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C. E Macdonald, A. C Wicks, and R. J Playford Final results from 10 year cohort of patients undergoing surveillance for Barrett's oesophagus: observational study BMJ, November 18, 2000; 321(7271): 1252 - 1255. [Abstract] [Full Text]
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C. A. Eads, R. V. Lord, S. K. Kurumboor, K. Wickramasinghe, M. L. Skinner, T. I. Long, J. H. Peters, T. R. DeMeester, K. D. Danenberg, P. V. Danenberg, et al. Fields of Aberrant CpG Island Hypermethylation in Barrett's Esophagus and Associated Adenocarcinoma Cancer Res., September 1, 2000; 60(18): 5021 - 5026. [Abstract] [Full Text]
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J. A. Jankowski, I. Perry, and R. F. Harrison Gastro-oesophageal cancer: death at the junction BMJ, August 19, 2000; 321(7259): 463 - 464. [Full Text]
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M. Pera, M. J. Brito, M. Pera, R. Poulsom, E. Riera, L. Grande, A. Hanby, and N. A. Wright Duodenal-content reflux esophagitis induces the development of glandular metaplasia and adenosquamous carcinoma in rats Carcinogenesis, August 1, 2000; 21(8): 1587 - 1591. [Abstract] [Full Text] [PDF]
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P. Murray, G Frampton, and P. Nelson Cell adhesion molecules BMJ, August 7, 1999; 319(7206): 332 - 334. [Full Text]
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