title: Altered expression of CD44 and DKK1 in the progression of Barrett's esophagus to esophageal adenocarcinoma.
abstract: Barrett's esophagus (BE) is an acquired condition in which the normal lining of the esophagus is replaced by intestinal metaplastic epithelium. BE can evolve to esophageal adenocarcinoma (EAC) through low-grade dysplasia (LGD) and high-grade dysplasia (HGD). The only generally accepted marker for increased risk of EAC is the presence of HGD, diagnosed on endoscopic biopsies. More specific markers for the prediction of EAC risk are needed. A tissue microarray was constructed comprising tissue samples from BE, LGD, HGD, and EAC. Marker expression was studied by immunohistochemistry using antibodies against CD44, DKK1, CDX2, COX2, SOX9, OCT1, E-cadherin, and beta-catenin. Immunostaining was evaluated semi-quantitatively. CD44 expression decreased in HGD and EAC relative to BE and LGD. DKK1 expression increased in HGD and EAC relative to BE and LDG. CDX2 expression increased in HGD but decreased in EAC. COX2 expression decreased in EAC, and SOX9 expression increased only in the upper crypt epithelial cells in HGD. E-cadherin expression decreased in EAC. Nuclear beta-catenin was not significantly different between BE, LGD, and HGD. Loss of CD44 and gain of DKK1 expression characterizes progression from BE and LGD to HGD and EAC, and their altered expression might indicate an increased risk for developing an EAC. This observation warrants inclusion of these immunohistochemically detectable markers in a study with a long patient follow-up.
authors.affiliation: Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Darlavoix
authors.forename: W
authors.initials: W
authors.lastname: Seelentag
authors.forename: P
authors.initials: P
authors.lastname: Yan
authors.forename: A
authors.initials: A
authors.lastname: Bachmann
authors.forename: F T
authors.initials: FT
authors.lastname: Bosman
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism*; D001471:Barrett Esophagus / Q000175:diagnosis / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D000071616:CDX2 Transcription Factor; D051546:Cyclooxygenase 2 / Q000378:metabolism; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D019085:Fluorescent Antibody Technique, Direct; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; C501126:DKK1 protein, human; D018398:Homeodomain Proteins; D018960:Hyaluronan Receptors; D036341:Intercellular Signaling Peptides and Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human