Gut Liver.  2017 Jan;11(1):38-46. 10.5009/gnl15535.

CpG Island Methylator Phenotype-High Colorectal Cancers and Their Prognostic Implications and Relationships with the Serrated Neoplasia Pathway

• Rhee YY
• Kim KJ
• Kang GH

• KMID: 2412153
• DOI: http://doi.org/10.5009/gnl15535

Abstract

The concept of a CpG island methylator phenotype (CIMP) was first introduced by Toyota and Issa to describe a subset of colorectal cancers (CRCs) with concurrent hypermethylation of multiple CpG island loci. The concept of CIMP as a molecular carcinogenesis mechanism was consolidated by the identification of the serrated neoplasia pathway, in which CIMP participates in the initiation and progression of serrated adenomas. Distinct clinicopathological and molecular features of CIMP-high (CIMP-H) CRCs have been characterized, including proximal colon location, older age of onset, female preponderance, and frequent associations of high-level microsatellite instability and BRAF mutations. CIMP-H CRCs arise in sessile or traditional serrated adenomas and thus tend to display the morphological characteristics of serrated adenomas, including epithelial serration, vesicular nuclei, and abundant cytoplasm. Both the frequent association of CIMP and poor prognosis and different responses of CRCs to adjuvant therapy depending on CIMP status indicate clinical implications. In this review, we present an overview of the literature documenting the relevant findings of CIMP-H CRCs and their relationships with the serrated neoplasia pathway.

Keyword

Colon cancer; Colorectal cancer; CpG island methylator henotype; Microsatellite instability; Serrated neoplasia

MeSH Terms

Adenocarcinoma/epidemiology/*genetics/pathology
Adenoma/epidemiology/*genetics/pathology
Age of Onset
Colorectal Neoplasms/epidemiology/*genetics/pathology
*CpG Islands
*DNA Methylation
Humans
Microsatellite Instability
Mutation
Phenotype
Prognosis
Proto-Oncogene Proteins B-raf/genetics
Sex Distribution
Proto-Oncogene Proteins B-raf