Activation of the BMP4 Pathway and Early Expression of CDX2 Characterize Non-specialized Columnar Metaplasia in a Human Model of Barrett's Esophagus

Daniel Castillo, Sonia Puig, Mar Iglesias, Agustín Seoane, Carme de Bolós, Vicente Munitiz, Pascual Parrilla, Laura Comerma, Richard Poulsom, Kausilia K. Krishnadath, Luís Grande, Manuel Pera

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Abstract

Background: A human model of gastroesophageal reflux disease was used to examine the contribution of a non-specialized columnar type of metaplasia (NSCM) and key molecular events (BMP4 and CDX2) in the development of Barrett's esophagus. Methods: Biopsies of the remnant esophagus from 18 patients undergoing esophagectomy with gastric preservation were taken at 6-36-month intervals postoperatively and examined for activation of the BMP pathway (BMP4/P-Smad 1/5/8) and CDX2 and CDX1 expression by imunohistochemistry, quantitative real-time PCR, Western blot, and in situ hybridization. Results: A short segment (mean 15. 6 mm) of NSCM was detected in 10 (56%) patients, with an increasing prevalence from 17% at 6 months to 62% at 36 months. Nuclear expression of P-Smad 1/5/8 in the squamous epithelium close to the anastomosis with strong expression in all epithelial cells of NSCM areas was found. Forty-eight (63%) biopsies with NSCM showed scattered nuclear expression of CDX2. Two cases showed isolated glands at 18, 24, and 36 months that fully expressed CDX2 and co-expressed CDX1. BMP4 mRNA and CDX2 mRNA levels were significantly greater in NSCM than in squamous epithelium. Conclusions: BMP4 activation in NSCM and early expression of CDX2 are involved in the columnar epithelial differentiation of Barrett's esophagus. © 2011 The Society for Surgery of the Alimentary Tract.
Original languageEnglish
Pages (from-to)227-237
JournalJournal of Gastrointestinal Surgery
Volume16
Issue number2
DOIs
Publication statusPublished - 1 Feb 2012

Keywords

  • Barrett's esophagus
  • BMP4
  • CDX1
  • CDX2
  • Columnar metaplasia

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