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Duodenal-content Reflux Into the Esophagus Leads to Expression of Cdx2 and Muc2 in Areas of Squamous Epithelium in Rats

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Journal of Gastrointestinal Surgery Aims and scope

Abstract

The molecular events responsible for the transdifferentiation of epithelial cells of the esophagus to a columnar cell type are not well understood. Cdx2 has been detected in Barrett’s esophagus, so we sought evidence of Cdx2 expression during the process of transdifferentiation of the esophageal squamous epithelium into a glandular phenotype. Thirty-two rats underwent an esophago-jejunostomy to produce esophagitis of 20, 25, 30, or 35 weeks of duration. The spectrum of esophageal lesions induced by chronic reflux was examined for expression of Cdx2 and Muc2 by immunohistochemistry. Five animals developed glandular metaplasia and adenosquamous carcinoma, two developed only glandular metaplasia, and two had adenosquamous carcinoma alone. Nuclear Cdx2 expression was detected in 57% (four of seven) and 43% (three of seven) of foci of glandular metaplasia and adenosquamous carcinomas, respectively. Cdx2 staining was detectable in some squamous and some mucus secreting cells. Perinuclear and perivacuolar staining of Muc2 was detected focally in 71% (five of seven) and 57% (four of seven) of areas with glandular metaplasia and adenosquamous carcinoma, respectively. We show that duodenal-content reflux into the esophagus switches on the expression of Cdx2 protein in esophageal keratinocytic cells, promoting a mucinous transdifferentiation process with secretion of intestinal mucin Muc2.

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Acknowledgements

We wish to thank Dr. G.C. Hansson, Department of Medical Biochemistry, Goteborg University, Sweden, for kindly providing us with the anti-rat Muc2 polyclonal antibody and Dr. Antonio Martinez and Marta Garrido for technical assistance.

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Authors and Affiliations

  1. Section of Gastrointestinal Surgery, Hospital Universitario del Mar, IMIM, Passeig Marítim 25-29, 08003, Barcelona, Spain

    Manuel Pera, Miguel Pera & Luis Grande

  2. Unit of Cellular and Molecular Biology, IMIM, Barcelona, Spain

    Carmen de Bolós

  3. Department of Pathology, Hospital Garcia de Orta, Almada, Portugal

    Maria J. Brito

  4. Department of Pathology, Hospital Clínic, Barcelona, Spain

    Antonio Palacín & Antonio Cardesa

  5. Histopathology Unit, Cancer Research UK, London Research Institute, London, UK

    Richard Poulsom

Authors
  1. Manuel Pera
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  2. Miguel Pera
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  3. Carmen de Bolós
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  4. Maria J. Brito
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  5. Antonio Palacín
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  6. Luis Grande
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  7. Antonio Cardesa
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  8. Richard Poulsom
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Corresponding author

Correspondence to Manuel Pera.

Additional information

This work was supported by grant from the Fundació “La Caixa” (LC 02/126-00) and by grant Red de Centros 02/03, Instituto de Salud Carlos III, Spain

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Pera, M., Pera, M., de Bolós, C. et al. Duodenal-content Reflux Into the Esophagus Leads to Expression of Cdx2 and Muc2 in Areas of Squamous Epithelium in Rats. J Gastrointest Surg 11, 869–874 (2007). https://doi.org/10.1007/s11605-007-0162-7

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  • DOI: https://doi.org/10.1007/s11605-007-0162-7

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