Radiofrequency ablation for dysplasia in Barrett's esophagus restores β-catenin activation within esophageal progenitor cells

K. Krishnan, S. Komanduri, J. Cluley, R. Dirisina, P. Sinh, Jeff Z. Ko, L. Li, R. B. Katzman, T. A. Barrett

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Background and Aims: Endoscopic therapies for Barrett's esophagus (BE) associated dysplasia, particularly radiofrequency ablation (RFA), are popular alternatives to surgery. The effect of such therapies on dysplastic stem/progenitor cells (SPC) is unknown. Recent studies suggest that AKT phosphorylation of β-Catenin occurs in SPCs and may be a marker of activated SPCs. We evaluate the effect of RFA in restoring AKT-mediated β-Catenin signaling in regenerative epithelium. Methods: Biopsies were taken from squamous, non-dysplastic BE, dysplastic BE and esophageal adenocarcinoma (EAC). Also, post-RFA, biopsies of endoscopically normal appearing neosquamous epithelium were taken at 3, 6, and 12 months after successful RFA. Immunohistochemistry and Western blot analysis was performed for Pβ-Catenin 552 (Akt-mediated phosphorylation of β-Catenin), Ki-67 and p53. Results: There was no difference in Pβ-Catenin552 in squamous, GERD, small bowel and non-dysplastic BE. There was a fivefold increase in Pβ-Catenin 552 in dysplasia and EAC compared to non-dysplastic BE (P < 0.05). Also, there was a persistent threefold increase in Pβ-Catenin 552 in neosquamous epithelium 3 months after RFA compared to native squamous epithelium (P < 0.05) that correlated with increased Ki-67. Six months after RFA, Pβ-Catenin 552 and Ki-67 are similar to native squamous epithelium. Conclusions: Enhanced AKT-mediated β-Catenin activation is seen in BE-associated carcinogenesis. Three months after RFA, squamous epithelial growth from SPC populations exhibited increased levels of Pβ-Catenin 552. This epithelial response becomes quiescent at 6 months after RFA. These data suggest that elevated Pβ-Catenin 552 after RFA denotes a repair response in the neosquamous epithelium 3 months post-RFA.

Original languageEnglish (US)
Pages (from-to)294-302
Number of pages9
JournalDigestive Diseases and Sciences
Volume57
Issue number2
DOIs
StatePublished - Feb 2012

Keywords

  • AKT
  • Barrett's esophagus
  • Dysplasia
  • Radiofrequency ablation
  • Squamous epithelialium
  • Stem/progenitor cell
  • β-Catenin

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

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