Bethesda guidelines:: Relation to microsatellite instability and MLH1 promoter methylation in patients with colorectal cancer
Bethesda guidelines:: Relation to microsatellite instability and MLH1 promoter methylation in patients with colorectal cancer
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DOI：
10.7326/0003-4819-135-8_part_1-200110160-00007
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发表时间：
2001-10-16
影响因子：
39.2
通讯作者：
Zeuzem, S
中科院分区：
文献类型：
--
作者：
Raedle, J;Trojan, J;Zeuzem, S
背景：微卫星不稳定性是遗传性非息肉病性结直肠癌错配修复缺陷的一个特征，是错配修复基因MLH1或MSH2突变或与DNA甲基化相关的基因失活所致。贝塞斯达指南的建立是为了确定需要进行微卫星不稳定性测试的结直肠癌患者。目的：评估贝塞斯达微卫星不稳定性检测指南，并确定MLH1启动子甲基化在结直肠癌中的作用。设计：前瞻性队列研究。地点：德国法兰克福的三级护理转诊中心。患者：125名连续的结直肠癌患者。测量方法：根据贝塞斯达指南对患者进行评估，并对肿瘤标本进行微卫星不稳定性分析。对微卫星不稳定性患者进行MLH1启动子甲基化和MLH1和MSH2胚系突变检测。结果：在符合Bethesda指南标准的58例患者中有17例检测到微卫星不稳定性，在67例不符合标准的患者中检测到5例微卫星不稳定性。在符合Bethesda指南的17例微卫星不稳定性患者中，发现MLH1(n=3)、MSH2(n=7)或MLH1和MSH2混合突变(n=1)。在不符合Bethesda指南的微卫星不稳定性患者中，未观察到突变；11例MLH1或MSH2突变患者中有6例观察到MLH1启动子甲基化，11例无MLH1或MSH2突变患者中有5例MLH1启动子甲基化。结论：Bethesda指南可用于筛选微卫星不稳定性检测患者。MLH1和MSH2检测应推荐用于所有符合至少一项Bethesda标准的结直肠癌和微卫星不稳定患者。具有错配修复基因缺陷的结直肠癌患者，MLH1启动子甲基化可能伴随而不是启动癌变。
Background: Microsatellite instability is a hallmark of mismatch repair deficiency in hereditary nonpolyposis colorectal cancer and results from mutations in the mismatch repair genes MLH1 or MSH2 or from gene inactivation associated with DNA methylation. The Bethesda guidelines were established to identify patients with colorectal cancer who should be tested for microsatellite instability.Objective: To assess the Bethesda guidelines for detection, of microsatellite instability and to determine the role of MLH1 promoter methylation in colorectal cancer.Design: Prospective cohort study.Setting: Tertiary care referral center in Frankfurt, Germany.Patients: 125 consecutive patients with colorectal cancer.Measurements, Patients were assessed according to the Bethesda guidelines, and tumor specimens were analyzed for micro-satellite instability. Patients with microsatellite Instability were tested for MLH1 promoter methylation and MLH1 and MSH2 germline mutations. Results: Microsatellite instability was detected in 17 of 58 patients who fulfilled and 5 of 67 patients who did not fulfill criteria of the Bethesda guidelines. In I I of 17 patients with microsatellite instability who fulfilled Bethesda guidelines, an MLH1 (n = 3), MSH2 (n = 7), or combined MLH1 and MSH2 (n = 1) mutation was found. Among the patients with microsatellite instability who did not fulfill Bethesda guidelines, no mutations were observed; MLH1 promoter methylation was observed in 6 of 11 patients with an MLH1 or MSH2 mutation and 5 of 11 patients without an MLH1 or MSH2 mutation.Conclusions: The Bethesda guidelines are useful for selecting patients for microsatellite instability testing. MLH1 and MSH2 testing should be recommended in all patients with colorectal cancer and microsatellite instability who fulfill at least one Bethesda criterion. MLH1 promoter methylation may accompany rather than initiate carcinogenesis in patients with colorectal cancer who have mismatch repair gene defects.