Department of Pathology, National Cancer Center, Goyang, Gyeonggi-do, South Korea.
Virchows Arch. 2010 Oct;457(4):415-22. doi: 10.1007/s00428-010-0962-0. Epub 2010 Aug 25.
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.
胃癌（GC）是一种常见的人类癌症，其启动子 CpG 岛过度甲基化频繁发生。CpG 岛甲基化表型（CIMP）是指一组具有多个启动子 CpG 岛位置一致性甲基化的 GC。然而，对于 CIMP 阳性（CIMP-high）GC 的临床病理特征知之甚少。我们的研究旨在描述 CIMP-high GC 的临床病理特征。我们使用 MethyLight 测定法分析了 196 例 GC 的 16 个癌症特异性 CpG 岛位置的甲基化状态，并将 CIMP-high GC 定义为在 13 个或更多 CpG 岛位置发生甲基化的 GC。排除微卫星不稳定阳性 GC 和 EBV 阳性 GC 后，CIMP-high GC（n=10，6.7%）表现出较高的癌症分期、浸润性生长类型、分化不良以及 Lauren 分类中的弥漫型或混合型。与 CIMP-negative GC 相比，CIMP-high GC 的生存时间明显缩短。当 CIMP-negative GC（甲基化在 12 个或更少）被分为 CIMP-intermediate 和 CIMP-low（甲基化在 1 个或无）时，CIMP-low 的临床结果优于 CIMP-intermediate。14 个或更多 CpG 岛的过度甲基化与不良的临床结局密切相关，被认为是一个独立的预后因素。我们的研究结果表明，CIMP-high GC 具有特征性的临床病理参数，包括预后不良，与以前的研究不同。需要进行更广泛、大规模的研究来验证本研究的结果。
