Activation of pro-oncogenic pathways in colorectal hyperplastic polyps

BMC Cancer. 2013 Nov 8:13:531. doi: 10.1186/1471-2407-13-531.

Abstract

Background: In contrast to sessile serrated adenomas and traditional serrated adenomas which are associated with a significant cancer risk, the role of hyperplastic polyps (HP) in colorectal carcinogenesis as well as the molecular mechanisms underlying their development remain controversial and still need to be clarified. Several reports suggest that a subset of HP may represent precursor lesions of some colorectal cancers. However, biomarkers are needed to identify the subset of HP that may have a malignant potential. The hormone precursor, progastrin (PG) has been involved in colon carcinogenesis and is known to activate pro-oncogenic pathways such as the ERK or the STAT3 pathway. We therefore analyzed PG expression and the activation of these signaling factors in HP.

Methods: We retrospectively analyzed PG expression as well as the phosphorylation of ERK and STAT3 by immunohistochemistry in HP from 48 patients.

Results: Mean percentages of epithelial cells positive for PG or phospho-ERK were respectively, 31% and 33% in HP and were significantly higher in these lesions compared to normal colon (3%, p=0.0021 and 7%, p=0.0008, respectively). We found a significant correlation between PG and phospho-ERK expression in HP with ERK activation significantly stronger in lesions with high progastrin expression (p=0.015). In contrast, STAT3 was not significantly activated in HP compared to normal colon and we did not observe a significant correlation with PG expression.

Conclusions: HP overexpressing PG that have the highest activation of the ERK pathway might reflect less latent lesions that might have a malignant potential.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / genetics
  • Adenoma / metabolism
  • Adenoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Colonic Polyps / genetics
  • Colonic Polyps / metabolism*
  • Colonic Polyps / pathology
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Gastrins / genetics
  • Gastrins / metabolism
  • Humans
  • Hyperplasia
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Male
  • Middle Aged
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism*
  • Protein Precursors / genetics
  • Protein Precursors / metabolism
  • Retrospective Studies
  • Risk Factors
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction*

Substances

  • Gastrins
  • Oncogene Proteins
  • Protein Precursors
  • STAT3 Transcription Factor
  • big gastrin
  • Extracellular Signal-Regulated MAP Kinases