TY - JOUR
T1 - Molecular evolution of the metaplasia-dysplasia-adenocarcinoma sequence in the esophagus
AU - Jankowski, Janusz A.
AU - Wright, Nick A.
AU - Meltzer, Stephen J.
AU - Triadafilopoulos, George
AU - Geboes, Karl
AU - Casson, Alan G.
AU - Kerr, David
AU - Young, Lawrence S.
N1 - Funding Information:
Supported by grants from the U.S. Department of Veterans Affairs, the National Institutes of Health, the Imperial Cancer Research Fund (UK), and the Cancer Research Campaign (UK).
PY - 1999/4
Y1 - 1999/4
N2 - 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.
AB - 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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U2 - 10.1016/S0002-9440(10)65346-1
DO - 10.1016/S0002-9440(10)65346-1
M3 - Review article
C2 - 10233832
AN - SCOPUS:0032954422
SN - 0002-9440
VL - 154
SP - 965
EP - 973
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 4
ER -