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Arch Pathol Lab Med. 2008 Oct;132(10):1657-65. doi: 10.1043/1543-2165(2008)132[1657:CIMPIC]2.0.CO;2.

CpG island methylator phenotype in colorectal cancers: comparison of the new and classic CpG island methylator phenotype marker panels.

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  • 1Department of Pathology, Kyung Hee University College of Medicine, Seoul, Korea.

Abstract

CONTEXT:

CpG island methylator phenotype (CIMP) designates a subset of colorectal cancers featuring concordant hypermethylation of multiple promoter CpG islands. Little is known about the clinical outcome or histologic characteristics of CIMP-positive colorectal cancers defined by recently identified CpG island methylator phenotype panels.

OBJECTIVE:

To investigate and compare the molecular and clinicopathologic features of CIMP-positive colorectal cancers defined by classic (p16, hMLH1, MINT1, MINT2, MINT31) and new (CACNA1G, IGF2, NEUROG1, RUNX3, SOCS1) CIMP panels.

DESIGN:

We analyzed 130 colorectal cancers for hypermethylation of both panels using methylation-specific polymerase chain reaction.

RESULTS:

With at least 2 markers methylated, both classic (39/130; 23.1%) and new (23.1%) CIMP-positive colorectal cancers were significantly associated with proximal tumor location, microsatellite instability, and BRAF mutation (all P values were less than .05). The new panel outperformed the classic panel in detecting these features. With at least 3 markers methylated, new CIMP-positive colorectal cancers (16.9%) were closely associated with proximal tumor location, low frequency of KRAS mutation, and high frequency of BRAF mutation (all P values were less than .05), whereas classic CIMP-positive colorectal cancers (18.5%) were closely associated with proximal tumor location, frequent microsatellite instability, and frequent BRAF mutation (all P values were less than .05). Analyzing a combination of CIMP and microsatellite instability status, CIMP-positive/microsatellite instability-negative colorectal cancers had the worst clinical outcomes.

CONCLUSIONS:

Whereas the classic panel outperformed in predicting clinical outcome, the new panel was superior in detecting known clinicopathologic features of CIMP but inferior in prognostication power.

[PubMed - indexed for MEDLINE]
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