Microsatellite instability caused by hMLH1 promoter methylation increases with tumor progression in right-sided sporadic colorectal cancer
Microsatellite instability caused by hMLH1 promoter methylation increases with tumor progression in right-sided sporadic colorectal cancer
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DOI：
10.1159/000089768
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发表时间：
2005-01-01
期刊：
影响因子：
3.5
通讯作者：
Miki, Y
中科院分区：
文献类型：
--
作者：
Noda, H;Kato, Y;Miki, Y
目的：散发性结直肠癌 (SCRC) 的一部分表现出微卫星不稳定性 (MSI)。 SCRC 中的大多数 MSI 是由启动子甲基化导致的 hMLH1 失活引起的。然而，MSI 在 SCRC 进展中的作用仍不清楚。方法：32 例粘膜内癌和 63 例粘膜下浸润癌被分配到第 1 组（早期癌症），30 例 Dukes' B 癌和 26 例 Dukes' C 癌被分配到第 2 组（晚期癌症）。 hMLH1 启动子甲基化状态通过甲基化特异性 PCR 测定。 MSI 使用五种标记物确定。 hMLH1 表达通过免疫组织化学测定。结果：第1组95个肿瘤中有1个（1.1%）发现MSI，而第2组56个肿瘤中有4个（7.1%）发现MSI。在右侧肿瘤中，第1组hMLH1甲基化阳性肿瘤的总体频率与第2组没有显着差异（43个中17个，39.5%，23个中9个，39.1%）。在 hMLH1 启动子甲基化的右侧肿瘤中，第 1 组中 MSI 阳性肿瘤的频率显着低于第 2 组（17 个中有 1 个，5.9%；9 个中有 4 个，44.4%，p = 0.0081）。结论：在右侧 SCRC 中，hMLH1 启动子甲基化引起的 MSI 频率随着肿瘤进展而增加。版权所有 (C) 2005 S. Karger AG，巴塞尔。
Objective: A subset of sporadic colorectal cancers (SCRCs) exhibits microsatellite instability (MSI). Most MSI in SCRCs is caused by hMLH1 inactivation due to promoter methylation. However, the role of MSI in the progression of SCRCs remains unclear. Methods: Thirty-two intramucosal cancers and 63 cancers with submucosal invasion were assigned to group 1 ( early-stage cancer), and 30 Dukes' B and 26 Dukes' C cancers to group 2 ( advanced-stage cancer). hMLH1 promoter methylation status was determined by methylation-specific PCR. MSI was determined using five markers. hMLH1 expression was determined immunohistochemically. Results: MSI was found in 1 of 95 (1.1%) tumors in group 1, compared with 4 of 56 (7.1%) tumors in group 2. In right-sided tumors, the overall frequency of hMLH1 methylation- positive tumors in group 1 was not significantly different from that in group 2 ( 17 of 43, 39.5%, vs. 9 of 23, 39.1%). In right-sided tumors with hMLH1 promoter methylation, the frequency of MSI-positive tumors in group 1 was significantly lower than that in group 2 ( 1 of 17, 5.9%, vs. 4 of 9, 44.4%, p = 0.0081). Conclusion: The frequency of MSI caused by hMLH1 promoter methylation increases with tumor progression in right-sided SCRCs. Copyright (C) 2005 S. Karger AG, Basel.