Differential clinicopathological features in microsatellite instability-positive colorectal cancers depending on CIMP status
Differential clinicopathological features in microsatellite instability-positive colorectal cancers depending on CIMP status
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DOI：
10.1007/s00428-011-1080-3
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发表时间：
2011-07-01
期刊：
影响因子：
3.5
通讯作者：
Kang, Gyeong Hoon
中科院分区：
文献类型：
--
作者：
Bae, Jeong Mo;Kim, Mi Jung;Kang, Gyeong Hoon
微卫星不稳定性阳性（MSI+）结直肠癌（crc）分为CpG岛甲基化表型阳性（CIMP+）和CpG岛甲基化表型阴性（CIMP-）肿瘤。CIMP+/MSI+ crc的失活基因库与CIMP-/MSI+ crc重叠，但可能与CIMP-/MSI+ crc不同。由于表观遗传型差异很可能表现为表型差异，因此CIMP+/MSI+ crc与CIMP-/MSI+ crc在某些临床病理特征上可能存在差异。本研究旨在描述两种亚型之间的共同特征和不同特征。使用MethyLight法分析了8个CIMP面板标记物中72个MSI+ crc的甲基化状态。比较CIMP+/MSI+和CIMP-/MSI+的临床病理特征和KRAS/BRAF突变。我们分析了一组独立的MSI+ crc （n = 97）的CIMP+状态与临床结果的关系。CIMP+ 18例（25%），且CIMP+亚型与年龄高度相关（P < 0.001）。仅在CIMP-/MSI+ crc中观察到息肉样样外观，无溃疡（18.5%,P = 0.057）。CIMP+/MSI+亚型与分化差、髓样样、印戒细胞样和腺泡样样密切相关，而CIMP-/MSI+亚型与腺内嗜酸性粘蛋白和层状核密切相关（均P值< 0.05）。CIMP+/MSI+ crc患者的总生存率低于CIMP-/MSI+ crc患者。我们的研究结果表明，MSI+ crc的临床病理特征存在异质性，这取决于CIMP状态。观察到CIMP+和CIMP-亚型表现出不同的临床行为，可能为建立针对这两种亚型的特异性治疗策略提供线索。
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.