title: Cdx2 expression and its promoter methylation during metaplasia-dysplasia-carcinoma sequence in Barrett's esophagus.
abstract: OBJECTIVE
  To examine how the expression of caudal type homebox transcription factor 2 (Cdx2) is regulated in the development of malignancy in Barrett's esophagus.
  
  
  METHODS
  Cdx2, mucin (MUC) series (MUC2, MUC5AC and MUC6), p53 and E-cadherin expression in Barrett's esophagus and adenocarcinoma specimens were examined by immunostaining. Isolated clusters of cells from (1) MUC2 and Cdx2-positive intestinal metaplastic mucosa; (2) MUC5AC and MUC6-positive, and MUC2 and Cdx2-negative high-grade dysplasia (HD), or intramucosal adenocarcinoma (IMC); and (3) MUC5AC, MUC6 and Cdx2-positive poorly-differentiated invasive adenocarcinoma (PDA) were analyzed by methylation-specific polymerase chain reaction using sets of primers for detecting methylation status of the Cdx2 gene.
  
  
  RESULTS
  Most of the non-neoplastic Barrett's esophageal mucosa showing intestinal-type metaplasia with or without low-grade dysplasia was positive for E-cadherin, MUC series and Cdx2, but negative for p53. A portion of the low-grade to HD was positive for E-cadherin, MUC5AC, MUC6 and p53, but negative for MUC2 and Cdx2. The definite IMC area was strongly positive for MUC5AC, MUC6 and p53, but negative for MUC2 and Cdx2. Methylation of the Cdx2 promoter was not observed in intestinal metaplasia, while hypermethylation of part of its promoter was observed in hot dipped and IMC. Hypermethylation of a large fraction of the Cdx2 promoter was observed in PDA.
  
  
  CONCLUSIONS
  Cdx2 expression is restored irrespective of the methylation status of its promoter. Apparent positive immunohistochemical results can be a molecular mark for gene silencing memory.
authors: Division of Molecular Pathology, Ehime University Graduate School of Medicine, Toon 791-0295, Japan.
authors: Kenji
authors: K
authors: Makita
authors: Riko
authors: R
authors: Kitazawa
authors: Shuho
authors: S
authors: Semba
authors: Koto
authors: K
authors: Fujiishi
authors: Miku
authors: M
authors: Nakagawa
authors: Ryuma
authors: R
authors: Haraguchi
authors: Sohei
authors: S
authors: Kitazawa
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001706:Biopsy; D000071616:CDX2 Transcription Factor; D019175:DNA Methylation; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D004947:Esophagus / Q000737:chemistry* / Q000473:pathology; D018398:Homeodomain Proteins / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008679:Metaplasia; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic
chemical_list: D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins
keywords: Barrett¡’s esophagus; Caudal type homebox transcription factor 2; Intestinal metaplasia; Promoter hypermethylation
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