title: CpG island hypermethylator phenotype in gastric carcinoma and its clinicopathological features.
abstract: Gastric carcinoma (GC) is one of the human cancers in which promoter CpG island hypermethylation is frequently found. CpG island methylator phenotype (CIMP) refers to a subset of GCs which harbor concordant methylation of multiple promoter CpG island loci. However, little is known regarding clinicopathological features of CIMP-positive (CIMP-high) GC. Our study aimed to characterize clinicopathological features of CIMP-high GC. We analyzed 196 cases of GCs for their methylation status in 16 cancer-specific CpG island loci using MethyLight assay and arbitrarily defined CIMP-high GC as those with methylation at 13 or more CpG island loci. With exclusion of microsatellite instability-positive GC and EBV-positive GC from the analysis, CIMP-high GC (n = 10, 6.7%) demonstrated tendency toward higher cancer stage, infiltrative growth type, poor differentiation, and diffuse or mixed type of Lauren classification. CIMP-high GC showed significantly shortened survival compared with that of CIMP-negative GC. When CIMP-negative GC (methylation at 12 or less) was divided into CIMP-intermediate and CIMP-low (methylation at one or none), CIMP-low exhibited better clinical outcome than CIMP-intermediate. Hypermethylation at 14 CpG island loci or more was closely associated with poor clinical outcome and found to be an independent prognostic factor. Our findings that CIMP-high GCs were featured with characteristic clinicopathological parameters, including poor prognosis are distinct from previous studies. More extensive, large-scaled study is necessary to validate the findings of the present study.
authors.affiliation: Department of Pathology, National Cancer Center, Goyang, Gyeonggi-do, South Korea.
authors.forename: Seog-Yun
authors.initials: SY
authors.lastname: Park
authors.forename: Myeong Cherl
authors.initials: MC
authors.lastname: Kook
authors.forename: Young Woo
authors.initials: YW
authors.lastname: Kim
authors.forename: Nam-Yun
authors.initials: NY
authors.lastname: Cho
authors.forename: Namhee
authors.initials: N
authors.lastname: Jung
authors.forename: Hyeong-Ju
authors.initials: HJ
authors.lastname: Kwon
authors.forename: Tae-You
authors.initials: TY
authors.lastname: Kim
authors.forename: Gyeong Hoon
authors.initials: GH
authors.lastname: Kang
mesh_terms: D000328:Adult; D000368:Aged; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology