title: Radiofrequency ablation for dysplasia in Barrett's esophagus restores β-catenin activation within esophageal progenitor cells.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, Northwestern University Feinberg School of Medicine, 676 N. St. Clair, Suite 1400, Chicago, IL 60611, USA. k-krishnan@northwestern.edu
authors.forename: K
authors.initials: K
authors.lastname: Krishnan
authors.forename: S
authors.initials: S
authors.lastname: Komanduri
authors.forename: J
authors.initials: J
authors.lastname: Cluley
authors.forename: R
authors.initials: R
authors.lastname: Dirisina
authors.forename: P
authors.initials: P
authors.lastname: Sinh
authors.forename: Jeff Z
authors.initials: JZ
authors.lastname: Ko
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: R B
authors.initials: RB
authors.lastname: Katzman
authors.forename: T A
authors.initials: TA
authors.lastname: Barrett
mesh_terms: D000328:Adult; D001471:Barrett Esophagus / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery*; D015153:Blotting, Western; D017115:Catheter Ablation; D004848:Epithelium / Q000378:metabolism; D004947:Esophagus / Q000166:cytology*; D006801:Humans; D007150:Immunohistochemistry; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D013234:Stem Cells / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; D051057:Proto-Oncogene Proteins c-akt