Comparative assessment of three methods to analyze MGMT methylation status in a series of 350 gliomas and gangliogliomas.
Comparative assessment of three methods to analyze MGMT methylation status in a series of 350 gliomas and gangliogliomas.
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对分析 350 个神经胶质瘤和神经节胶质瘤系列中 MGMT 甲基化状态的三种方法进行比较评估。
DOI：
10.1016/j.prp.2017.10.007
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发表时间：
2017-12
期刊：
影响因子：
--
通讯作者：
leiming wang
中科院分区：
文献类型：
--
作者：
leiming wang
MGMT启动子甲基化被认为是胶质母细胞瘤对化疗和放疗反应的预后和预测生物标志物。许多不同的方法和平台，包括焦磷酸测序（PSQ），定量甲基化特异性PCR（qMSP）和免疫组织化学（IHC），甲基化敏感的高分辨率熔解（MS-HRM）和NGS（下一代测序）已被用于检测胶质瘤中的MGMT启动子甲基化。然而，关于分析MGMT状态的最合适方法仍然存在争议。采用PSQ、qMSP和IHC平行检测了350例神经胶质瘤和神经节细胞胶质瘤的MGMT启动子甲基化状态。以PSQ作为推荐的标准方法，计算灵敏度、特异性、阳性/阴性预测值以及与其他检测方法的相关性。在350例胶质瘤和神经节细胞胶质瘤中，PSQ、qMSP和IHC检测MGMT启动子甲基化的阳性率分别为53.1%、55.4%和70.3%。qMSP诊断胃癌的敏感性为97.8%，特异性为92.7%。根据PSQ，使用qMSP检测甲基化阳性的12例为阴性，根据qMSP检测阴性的4例为阳性。PSQ与qMSP的符合率为90.8%。免疫组化检测MGMT蛋白水平的敏感性和特异性分别为84.4%和45.7%。PSQ与IHC的符合率为30.8%。本研究表明，qMSP是一种有效和快速的检测方法，用于常规使用的病理实验室鉴定MGMT启动子甲基化。IHC和qMSP测定的组合可以为MGMT状态的预测提供高灵敏度和特异性。经qMSP和测序证实，少数PSQ检测阴性的病例确实存在MGMT启动子甲基化，该亚组患者可能从替莫唑胺中获益。
MGMT promoter methylation is considered as a prognostic and predictive biomarker indicating response to chemotherapy and radiotherapy in glioblastoma. A number of different methods and platforms including pyrosequencing (PSQ), quantitative methylation-specific PCR (qMSP) and immunohistochemistry (IHC), methylation-sensitive high resolution melting (MS-HRM) and NGS (Next Generation Sequencing) have been used to detect MGMT promoter methylation in gliomas. However, controversy remains about the most appropriate method to use for analyzing MGMT status. The MGMT promoter methylation status of a total of 350 gliomas and gangliogliomas was examined using PSQ, qMSP and IHC in parallel. Using PSQ as a recommended standard method, the sensitivity, specificity, positive/negative predictive value and correlation with the other assays were calculated. Among 350 glioma and ganglioglioma cases, the MGMT promoter tested positive for methylation in 53.1%, 55.4%, and 70.3% of the cases by PSQ, qMSP and IHC, respectively. The sensitivity and specificity of qMSP were 97.8% and 92.7%, respectively. Twelve cases that tested positive for methylation using qMSP were negative according to PSQ, and four cases that were negative according to qMSP tested positive according to PSQ. The concordance rate between PSQ and qMSP was 90.8%. The sensitivity and specificity of IHC for the detection of MGMT at the protein level were 84.4% and 45.7%, respectively. The concordance rate between PSQ and IHC was 30.8%. This study demonstrated that qMSP is an effective and rapid detection method for routine use in pathology laboratories for the identification of MGMT promoter methylation. A combination of IHC and qMSP assays can provide high sensitivity and specificity for the prediction of MGMT status. A few cases that tested negative with PSQ did harbor MGMT promoter methylation, as confirmed by qMSP and sequencing, and this subgroup of patients may benefit from temozolomide.
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影响因子：
158.5
作者：
Stupp, R;Mason, WP;Ryan, G
通讯作者：
Ryan, G
DOI：
10.1016/s1040-1741(08)70253-7
发表时间：
2006
期刊：
Yearbook of Oncology
影响因子：
--
作者：
P. Loehrer
通讯作者：
P. Loehrer
影响因子：
4.1
作者：
Mikeska, Thomas;Bock, Christoph;Waha, Andreas
通讯作者：
Waha, Andreas
影响因子：
4.1
作者：
Cankovic, Milena;Nikiforova, Marina N.;Lee, Eudocia Q.
通讯作者：
Lee, Eudocia Q.
影响因子：
5.7
作者：
Switzeny OJ;Christmann M;Renovanz M;Giese A;Sommer C;Kaina B
通讯作者：
Kaina B