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  • Title: CpG island methylator phenotype in colorectal cancers: comparison of the new and classic CpG island methylator phenotype marker panels.
    Author: Lee S, Cho NY, Yoo EJ, Kim JH, Kang GH.
    Journal: Arch Pathol Lab Med; 2008 Oct; 132(10):1657-65. PubMed ID: 18834226.
    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.
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