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Conjoint Gastroenterology Laboratory, Clinical Research Centre, Royal Brisbane Hospital Research Foundation, Queensland 4029, Australia [V. L. J. W., C. V. A. W., M. D. W., L. A. S., J. Y., B. A. L.]; Division of Population Studies and Human Genetics, Queensland Institute of Medical Research, Queensland, Australia 4029 [D. P., N. P.]; University of Maryland, Baltimore, Baltimore, Maryland 21201 [S. J. M.]; and Department of Pathology, University of Queensland, Brisbane, Queensland, Australia 4006 [J. R. J.]
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 of p16INK4a, 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.
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