Morphological and molecular heterogeneity within nonmicrosatellite instability-high colorectal cancer.

Abstract:

: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 p16(INK4a), p14(ARF), 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.

journal_name

Cancer Res

journal_title

Cancer research

authors

Whitehall VL,Wynter CV,Walsh MD,Simms LA,Purdie D,Pandeya N,Young J,Meltzer SJ,Leggett BA,Jass JR

subject

Has Abstract

pub_date

2002-11-01 00:00:00

pages

6011-4

issue

21

eissn

0008-5472

issn

1538-7445

journal_volume

62

pub_type

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