Esophageal adenocarcinoma arising in Barrett esophagus.
The major risk factors for esophageal adenocarcinoma are gastroesophageal reflux disease (GERD) and Barrett esophagus, a squamous-to-columnar cell metaplasia that predisposes to malignancy. Adenocarcinomas in Barrett esophagus are thought to arise through a sequence of growth-promoting, genetic alterations that accumulate until the cells have acquired the physiologic hallmarks of cancer proposed by Hanahan and Weinberg. Moreover, GERD and Barrett esophagus are associated with chronic esophagitis, and inflammation is a well known risk factor for cancer formation. The cell that gives rise to Barrett metaplasia is not known. It has been proposed that the metaplasia may arise from a change in the differentiation pattern of stem cells that either reside in the esophagus or are recruited to the esophagus from the bone marrow. Alternatively, it is possible that Barrett metaplasia develops through the conversion of one differentiated cell type into another. Regardless of the cell of origin, Barrett metaplasia ultimately must be sustained by stem cells, which might be identified by intestinal stem cell markers. An emerging concept in tumor biology is that cancer stem cells are responsible for sustaining tumor growth. If Barrett cancers develop from Barrett stem cells, then a therapy targeted at those stem cells might prevent esophageal adenocarcinoma. This report reviews the risk factors for Barrett esophagus and esophageal adenocarcinoma, the mechanisms by which genetic alterations might contribute to carcinogenesis in Barrett esophagus, and the role of stem cells in the development of Barrett metaplasia and adenocarcinoma.
Zhang
Hui Ying
HY
Department of Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
Spechler
Stuart Jon
SJ
Souza
Rhonda F
RF
D000230:Adenocarcinoma / Q000209:etiology* / Q000473:pathology; D001471:Barrett Esophagus / Q000150:complications* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000209:etiology* / Q000473:pathology; D006801:Humans; D012307:Risk Factors; D013234:Stem Cells / Q000166:cytology