Morphological and molecular heterogeneity within nonmicrosatellite instability-high colorectal cancer

Vicki L.J. Whitehall, Coral V.A. Wynter, Michael D. Walsh, Lisa A. Simms, David Purdie, Nirmala Pandeya, Joanne Young, Stephen J. Meltzer, Barbara A. Leggett, Jeremy R. Jass

Research output: Contribution to journalArticlepeer-review


Colorectal cancer (CRC) has traditionally been classified into two groups: microsatellite stable/low-level instability (MSS/MSI-L) and high-level MSI (MSI-H) groups on the basis of multiple molecular and clinicopathologic criteria. Using methylated in tumor (MINT) markers 1, 2, 12, and 31, we stratified 77 primary CRCs into three groups: MINT++ (>2), MINT+ (1-2), and MINT- (0 markers methylated). The MSS/MSI-L/ MINT++ group was indistinguishable from the MSI-H/MINT++ group with respect to methylation ofp16INK4a, p14ARF, and RIZ1, and multiple morphological features. The only significant difference between MSI-H and non-MSI-H MINT++ cancers was the higher frequency of K-ras mutation (P < 0.004) and lower frequency of hMLH1 methylation (P < 0.001) in the latter. These data demonstrate that the separation of CRC into two nonoverlapping groups (MSI-H versus MSS/MSI-L) is a misleading oversimplification.

Original languageEnglish (US)
Pages (from-to)6011-6014
Number of pages4
JournalCancer Research
Issue number21
StatePublished - 2002
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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