Radiofrequency Ablation for Dysplasia in Barrett’s Esophagus Restores β-Catenin Activation Within Esophageal Progenitor Cells
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- Krishnan, K., Komanduri, S., Cluley, J. et al. Dig Dis Sci (2012) 57: 294. doi:10.1007/s10620-011-1899-0
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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.
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-Catenin552 (Akt-mediated phosphorylation of β-Catenin), Ki-67 and p53.
There was no difference in Pβ-Catenin552 in squamous, GERD, small bowel and non-dysplastic BE. There was a fivefold increase in Pβ-Catenin552 in dysplasia and EAC compared to non-dysplastic BE (P < 0.05). Also, there was a persistent threefold increase in Pβ-Catenin552 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-Catenin552 and Ki-67 are similar to native squamous epithelium.
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-Catenin552. This epithelial response becomes quiescent at 6 months after RFA. These data suggest that elevated Pβ-Catenin552 after RFA denotes a repair response in the neosquamous epithelium 3 months post-RFA.
KeywordsBarrett’s esophagus Radiofrequency ablation β-Catenin AKT Stem/progenitor cell Dysplasia Squamous epithelialium
Gastroesophageal reflux disease
High grade dysplasia