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Molecular Evolution of the Metaplasia-Dysplasia-Adenocarcinoma Sequence in the Esophagus
- Source :
- The American Journal of Pathology. 154:965-973
- Publication Year :
- 1999
- Publisher :
- Elsevier BV, 1999.
-
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.
- Subjects :
- Male
Pathology
medicine.medical_specialty
Esophageal Neoplasms
Review
Adenocarcinoma
Biology
medicine.disease_cause
Pathology and Forensic Medicine
Barrett Esophagus
Esophagus
Cell Movement
Metaplasia
medicine
Humans
Neoplasm Invasiveness
Esophagitis, Peptic
Esophageal disease
Genetic heterogeneity
Cadherin
Cell Cycle
Aneuploidy
medicine.disease
digestive system diseases
Clone Cells
Dysplasia
Catenin
Female
Tumor Suppressor Protein p53
medicine.symptom
Carcinogenesis
Subjects
Details
- ISSN :
- 00029440
- Volume :
- 154
- Database :
- OpenAIRE
- Journal :
- The American Journal of Pathology
- Accession number :
- edsair.doi.dedup.....a57fd62042a5eb0c5505b1470340fb68