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Over-expression of cathepsin E and trefoil factor 1 in sessile serrated adenomas of the colorectum identified by gene expression analysis

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Abstract

Sessile serrated adenomas are now recognised as precursor lesions of a substantial subset of colorectal cancers arising via a so-called “serrated pathway”. However, their biological markers remain to be defined. The aim of our study was to identify differentially expressed genes in sessile serrated adenomas and conventional adenomas. Gene expression analysis demonstrated molecular differences between polyp types. Further studies using quantitative real-time polymerase chain reaction on cathepsin E (CTSE) demonstrated a significantly (p < 0.05) higher expression in sessile serrated adenomas as compared to hyperplastic polyp and tubular adenomas. Trefoil Factor 1 showed the same trend of expression for sessile serrated adenomas as compared to hyperplastic polyps and was significantly higher in both polyps compared to tubular adenomas. Immunohistochemistry for both proteins demonstrated strong cytoplasmic staining of abnormal crypts in all sessile serrated adenomas, while staining in tubular adenomas and hyperplastic polyps was absent or weak and focal. BRAF and KRAS mutation analysis were employed to further validate polyp discrimination. The findings demonstrated the positive association of the BRAF mutation, V600E, with sessile serrated adenomas and KRAS mutations with tubular adenomas (p < 0.05). This study demonstrates the over-expression in CTSE, in particular, and TFF1 in sessile serrated adenomas compared to both hyperplastic polyps and tubular adenomas.

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Acknowledgements

The authors thank Kay Taylor, Gastroenterology Research Laboratory, SA Pathology, for her technical assistance with the immunohistochemistry and Nancy Brigs for her assistance with the statistical analysis. This study was supported by Cancer and Bowel Research Trust, SA, Australia.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Gastroenterology Research Laboratory, Surgical Pathology, SA Pathology, Adelaide, 5000, Australia

    Maria Caruso, Hiroyuki Takahashi & Andrew Ruszkiewicz

  2. Colorectal Surgery Unit, Royal Adelaide Hospital, Adelaide, 5000, Australia

    James Moore & Michelle Thomas

  3. Hanson Institute, SA Pathology, Adelaide, 5000, Australia

    Gregory J. Goodall & Anna Tyskin

  4. Division of Molecular Pathology, SA Pathology, Adelaide, 5000, Australia

    Stuart Phillis, Glenice Cheetham & Nancy Lerda

  5. Department of Medicine, The University of Adelaide, Adelaide, 5000, Australia

    Gregory J. Goodall

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  1. Maria Caruso
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Correspondence to Andrew Ruszkiewicz.

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Caruso, M., Moore, J., Goodall, G.J. et al. Over-expression of cathepsin E and trefoil factor 1 in sessile serrated adenomas of the colorectum identified by gene expression analysis. Virchows Arch 454, 291–302 (2009). https://doi.org/10.1007/s00428-009-0731-0

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  • DOI: https://doi.org/10.1007/s00428-009-0731-0

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