title: Differential clinicopathological features in microsatellite instability-positive colorectal cancers depending on CIMP status.
abstract: Microsatellite instability-positive (MSI+) colorectal cancers (CRCs) are divided into CpG island methylator phenotype-positive (CIMP+) and CpG island methylator phenotype-negative (CIMP-) tumors. The repertoire of inactivated genes in CIMP+/MSI+ CRCs overlaps with but is likely to differ from that of CIMP-/MSI+ CRCs. Because epigenotypic differences are likely to be manifested as phenotypic differences, CIMP+/MSI+ CRCs are expected to differ from CIMP-/MSI+ CRCs in some clinicopathological features. This study aimed to characterize both common and different features between the two subtypes. A total of 72 MSI+ CRCs were analyzed for their methylation status in eight CIMP panel markers using MethyLight assay. CIMP+/MSI+ and CIMP-/MSI+ CRCs were compared regarding clinicopathologic features and mutation in KRAS/BRAF. An independent set of MSI+ CRCs (n = 97) was analyzed for their relationship of CIMP+ status with clinical outcome. Eighteen cases (25%) were CIMP+, and this CIMP+ subtype was highly correlated with older age (P < 0.001). Polypoid gross appearance without ulceration was observed only in CIMP-/MSI+ CRCs (18.5%, P = 0.057). CIMP+/MSI+ CRCs were closely associated with poor differentiation, medullary appearance, signet ring cell appearance, and acinar-form appearance, whereas the CIMP-/MSI+ subtype was closely associated with intraglandular eosinophilic mucin and stratified nuclei (all P values <0.05). Patients with CIMP+/MSI+ CRCs showed worse overall survival than patients with CIMP-/MSI+ CRCs. Our results demonstrate heterogeneity in the clinicopathological features of MSI+ CRCs depending on CIMP status. The observation that CIMP+ and CIMP- subtypes showed different clinical behaviors may provide a clue for establishing subtype-specific therapeutic strategies for these two subtypes.
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744, South Korea.
authors.forename: Jeong Mo
authors.initials: JM
authors.lastname: Bae
authors.forename: Mi Jung
authors.initials: MJ
authors.lastname: Kim
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Kim
authors.forename: Jae Moon
authors.initials: JM
authors.lastname: Koh
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: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D015996:Survival Rate
chemical_list: D004273:DNA, Neoplasm; D005819:Genetic Markers