Conventional colon adenomas harbor various disturbances in microsatellite stability and contain micro-serrated foci with microsatellite instability

PLoS One. 2017 Feb 24;12(2):e0172381. doi: 10.1371/journal.pone.0172381. eCollection 2017.

Abstract

Introduction: Colorectal cancer belongs to the most frequent occurring malignancies. A prediction of the clinical outcome and appropriate choice of neoadjuvant chemotherapy needs personalized insight to the main driving pathways. Because most CRCs have polyps as progenitor lesions, studying the pathways driving to adenomagenesis is no less important.

Goals: Our purpose was the evaluation of microsatellite stability status within conventional colon adenomas and also β-catenin, BRAFV600E and p53 contribution.

Material and methods: The cohort included 101 cases of typical colon adenomas with high grade epithelial dysplasia according to WHO. An immunohistochemistry method was used for the depiction of the expression of targeted proteins, as also their heterogeneity.

Results: Generally, we noted a 10% frequency of MSI events where MSI-H reached a 5% share occurred within the left colon and rectal polyps. β-catenin nuclear overexpression was noted with a 70% frequency and p53 with close to a 24% frequency. In addition, we found a presence of micro-serration foci more often within tubular adenomas, where focal MSI took place more often. Our results indicate that MSI events occur more often than had been theorized earlier. It results in tumour heterogeneity, more complex underlying pathways and finally ontogenetic molecular-diversity of tumours besides similar occurring histopathological features.

MeSH terms

  • Adenoma / genetics*
  • Adenoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Colonic Polyps / genetics
  • Colonic Polyps / pathology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • DNA Methylation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Microsatellite Instability*
  • Middle Aged
  • Mutation
  • Proto-Oncogene Proteins B-raf / genetics*
  • Tumor Suppressor Protein p53 / genetics*
  • beta Catenin / biosynthesis*
  • beta Catenin / genetics

Substances

  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • beta Catenin
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf

Grants and funding

The study has been completely financed by the Statute Scientific Found (No. 615 515) of Jan Kochanowski University in Kielce, Poland.