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.
|Number of pages||9|
|Journal||Digestive Diseases and Sciences|
|State||Published - Feb 2012|
Bibliographical noteFunding Information:
Acknowledgments T. A. Barrett was supported by NIH, R01DK-54778 and R01DK-47073.
- Barrett's esophagus
- Radiofrequency ablation
- Squamous epithelialium
- Stem/progenitor cell
ASJC Scopus subject areas