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

Virchows Arch. 2009 Mar;454(3):291-302. doi: 10.1007/s00428-009-0731-0. Epub 2009 Jan 27.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / genetics*
  • Adenoma / metabolism
  • Adenoma / pathology
  • Aged
  • Biomarkers, Tumor / analysis*
  • Cathepsin E / biosynthesis*
  • Cathepsin E / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Intestinal Polyps / genetics
  • Intestinal Polyps / metabolism
  • Intestinal Polyps / pathology
  • Male
  • Mutation
  • Oligonucleotide Array Sequence Analysis
  • Precancerous Conditions / genetics
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / pathology
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins p21(ras)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trefoil Factor-1
  • Tumor Suppressor Proteins / biosynthesis*
  • Tumor Suppressor Proteins / genetics
  • Up-Regulation
  • ras Proteins / genetics


  • Biomarkers, Tumor
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • TFF1 protein, human
  • Trefoil Factor-1
  • Tumor Suppressor Proteins
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Cathepsin E
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins