Department of Neuropathology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Int J Cancer. 2012 Sep 15;131(6):1342-50. doi: 10.1002/ijc.27385. Epub 2012 Jan 11.
O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation identifies a subpopulation of glioblastoma patients with more favorable prognosis and predicts a benefit from alkylating agent chemotherapy (CT). Little is known about its prevalence and clinical significance in older glioblastoma patients. We studied 233 glioblastoma patients aged 70 years or more (144 males, 89 females, median age: 74 years, range: 70.0-86.6 years), who were prospectively enrolled in the German Glioma Network, for MGMT promoter methylation by methylation-specific PCR (MSP) in all patients and DNA pyrosequencing in 166 patients. MGMT data were correlated with patient outcome. Median progression-free survival (PFS) was 4.8 months (95% CI: 4.3-5.3) and median overall survival (OS) was 7.7 months (95% CI: 6.3-9.0). MGMT promoter methylation was detected by MSP in 134 patients (57.5%). For the whole cohort, PFS was 5.2 versus 4.7 months (p = 0.207) and OS was 8.4 versus 6.4 months (p = 0.031) in patients with versus without MGMT promoter methylation. Patients with MGMT methylated tumors had longer PFS when treated with radiotherapy (RT) plus CT or CT alone compared to patients treated with RT alone. Patients with MGMT unmethylated tumors appeared to derive no survival benefit from CT, regardless of whether given at diagnosis together with RT or as a salvage treatment. Patients treated with RT plus CT or CT alone demonstrated longer OS when pyrosequencing revealed >25% MGMT methylated alleles. Taken together, MGMT promoter methylation may be a useful biomarker to stratify elderly glioblastoma patients for treatment with versus without alkylating agent CT.
O(6)-甲基鸟嘌呤-DNA-甲基转移酶（MGMT）启动子甲基化鉴定出具有更有利预后的胶质母细胞瘤患者亚群，并预测烷化剂化疗（CT）的获益。在年龄较大的胶质母细胞瘤患者中，其患病率和临床意义知之甚少。我们前瞻性地研究了 233 名年龄在 70 岁或以上的胶质母细胞瘤患者（144 名男性，89 名女性，中位年龄：74 岁，范围：70.0-86.6 岁），所有患者均通过甲基化特异性 PCR（MSP）进行 MGMT 启动子甲基化检测，166 名患者进行 DNA 焦磷酸测序。MGMT 数据与患者预后相关。中位无进展生存期（PFS）为 4.8 个月（95%CI：4.3-5.3），中位总生存期（OS）为 7.7 个月（95%CI：6.3-9.0）。MSP 检测到 134 名患者（57.5%）MGMT 启动子甲基化。对于整个队列，有 MGMT 启动子甲基化的患者 PFS 为 5.2 个月，无 MGMT 启动子甲基化的患者为 4.7 个月（p=0.207），OS 为 8.4 个月，无 MGMT 启动子甲基化的患者为 6.4 个月（p=0.031）。接受放疗（RT）加 CT 或 CT 单独治疗的 MGMT 甲基化肿瘤患者的 PFS 较长，而仅接受 RT 治疗的患者则较短。MGMT 未甲基化肿瘤患者无论是否与 RT 一起作为诊断性治疗或作为挽救性治疗，均未从 CT 中获益。当焦磷酸测序显示>25%MGMT 甲基化等位基因时，接受 RT 加 CT 或 CT 单独治疗的患者 OS 更长。综上所述，MGMT 启动子甲基化可能是一种有用的生物标志物，可将老年胶质母细胞瘤患者分层为是否接受烷化剂 CT 治疗。
