Improved testing for microsatellite instability in colorectal cancer using a simplified 3-marker assay. Academic Article uri icon

Overview

abstract

  • BACKGROUND: In colorectal cancer (CRC), microsatellite instability (MSI) is a valuable marker of defective DNA mismatch repair that identifies cancers with distinct phenotypic properties, including favorable survival. However, the optimal assay for MSI status is unknown. We have evaluated a simplified 3-marker assay for MSI and compared it with the 5-marker (NCI) assay to see if technical variations in MSI testing are important. MATERIALS AND METHODS: DNA samples from 357 CRCs were evaluated for MSI using the 5 microsatellite markers recommended for the NCI assay (BAT 25, BAT26, D2S123, D5S346, and D17S250). Results were compared with a simplified 3-marker assay (BAT25, BAT26, and D2S123). CRCs identified as MSI were evaluated for their clinical, pathological, and genetic characteristics. RESULTS: The 5-marker assay identified 96 cancers as MSI. Only 56 of these were MSI by the 3-marker assay (3-marker+ group), leaving 40 cases identified as MSI only by NCI criteria (3-marker- group). The remaining 261 cancers were microsatellite stable (MSS). The 3-marker+ MSI tumors had features characteristic of MSI tumors: more proximal, poorly differentiated, associated with hereditary nonpolyposis colorectal cancer (HNPCC), more BRAF mutations, fewer KRAS mutations, better 5-year disease-specific survival, more frequent mismatch repair (MMR) protein loss, and less likely to be metastatic on presentation (P < .05). Chromosomal arm loss was observed only in 3-marker- MSI and MSS cancers (P < .05). CONCLUSION: The 3-marker MSI assay outperforms the traditional 5-marker assay for identifying patients with favorable prognosis and homogeneous clinical and genetic features. More accurate MSI testing should improve prognostic and predictive scoring systems for colorectal cancer.

publication date

  • August 12, 2010

Research

keywords

  • Adenocarcinoma
  • Biomarkers, Tumor
  • Colorectal Neoplasms
  • DNA Repair Enzymes
  • Germ-Line Mutation
  • Microsatellite Instability
  • Microsatellite Repeats

Identity

PubMed Central ID

  • PMC3269820

Scopus Document Identifier

  • 78650989829

Digital Object Identifier (DOI)

  • 10.1245/s10434-010-1147-4

PubMed ID

  • 20703819

Additional Document Info

volume

  • 17

issue

  • 12