title: Mixed-type gastric cancer and its association with high-frequency CpG island hypermethylation.
abstract: Gastric carcinoma (GC) is one of the human cancers in which promoter CpG island hypermethylation is frequently found. We used the MethyLight assay to evaluate the methylation status of 16 CpG island loci that are hypermethylated in GC. We analyzed the relationship between CpG island hypermethylation of these 16 genes and the clinicopathological features in 191 advanced GCs. A significant difference was observed between the number of methylated genes in Epstein-Barr virus (EBV)-negative and microsatellite instability (MSI)-negative GCs of different histological types (Lauren classification; P < 0.01). We found that mixed-type (MT) carcinomas, which have both diffuse-type (DT) and intestinal-type (IT) components, had more methylated genes (10.6) than either DT carcinomas (7.6 methylated genes) or IT carcinomas (6.7 methylated genes) (P < 0.001). This trend was also observed when EBV-positive or MSI-positive GCs were excluded from the analysis (9.2, 6.9, and 4.8; P < 0.001). When the IT and DT components were dissected from MT carcinomas and the methylation of these 16 genes was evaluated, both components had a number of methylated genes similar to MT carcinomas, (10.2 and 9.7, respectively), which was significantly higher than was found in IT and DT carcinomas (P < 0.05). These findings indicate that MT carcinoma is distinct from IT and DT carcinomas in its enhanced CpG island hypermethylation status and implicate the enhanced promoter CpG island hypermethylation in the histogenesis of MT carcinoma.
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: Tae-You
authors.initials: TY
authors.lastname: Kim
authors.forename: Gyeong Hoon
authors.initials: GH
authors.lastname: Kang
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins