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Radiofrequency Ablation for Dysplasia in Barrett’s Esophagus Restores β-Catenin Activation Within Esophageal Progenitor Cells

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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-Catenin552 (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-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.

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-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.

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Abbreviations

BE:

Barrett’s esophagus

EAC:

Esophageal adenocarcinoma

GERD:

Gastroesophageal reflux disease

SPC:

Stem/progenitor cell

RFA:

Radiofrequency ablation

HGD:

High grade dysplasia

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Acknowledgments

T. A. Barrett was supported by NIH, R01DK-54778 and R01DK-47073.

Conflict of interest

No conflicts of interest exist for any of the authors of this manuscript.

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Authors and Affiliations

  1. 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, S. Komanduri, R. Dirisina, P. Sinh, Jeff Z. Ko, R. B. Katzman & T. A. Barrett

  2. Department of Internal Medicine, Northwestern University, Chicago, IL, 60611, USA

    J. Cluley

  3. Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO, 64110, USA

    L. Li

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  1. K. Krishnan
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  2. S. Komanduri
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  3. J. Cluley
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  4. R. Dirisina
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  5. P. Sinh
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  6. Jeff Z. Ko
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  9. T. A. Barrett
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Correspondence to T. A. Barrett.

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Krishnan, K., Komanduri, S., Cluley, J. et al. Radiofrequency Ablation for Dysplasia in Barrett’s Esophagus Restores β-Catenin Activation Within Esophageal Progenitor Cells. Dig Dis Sci 57, 294–302 (2012). https://doi.org/10.1007/s10620-011-1899-0

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  • DOI: https://doi.org/10.1007/s10620-011-1899-0

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