Molecular evolution of the metaplasia-dysplasia-adenocarcinoma sequence in the esophagus

Janusz A. Jankowski, Nick A. Wright, Stephen J. Meltzer, George Triadafilopoulos, Karl Geboes, Alan G. Casson, David Kerr, Lawrence S. Young

Research output: Contribution to journalReview articlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)965-973
Number of pages9
JournalAmerican Journal of Pathology
Volume154
Issue number4
DOIs
StatePublished - Apr 1999

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'Molecular evolution of the metaplasia-dysplasia-adenocarcinoma sequence in the esophagus'. Together they form a unique fingerprint.

Cite this