O 6-Methylguanine DNA methyltransferase determined by promoter hypermethylation and immunohistochemical expression is correlated with progression-free survival in patients with glioblastoma
O 6-Methylguanine DNA methyltransferase determined by promoter hypermethylation and immunohistochemical expression is correlated with progression-free survival in patients with glioblastoma
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DOI：
10.1007/s10147-010-0065-6
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发表时间：
2010-08-01
影响因子：
3.3
通讯作者：
Tominaga, Teiji
中科院分区：
文献类型：
--
作者：
Sonoda, Yukihiko;Yokosawa, Michiko;Tominaga, Teiji
通过对一系列新诊断的胶质母细胞瘤患者的O（6）-甲基鸟嘌呤DNA甲基转移酶（MGMT）启动子甲基化和蛋白表达的分析，评估了MGMT的预后意义。从73例患者中的62例获得的冷冻手术标本中分离基因组DNA。甲基化特异性聚合酶链反应测定MGMT启动子甲基化。与其他已知的预后因素一起评估MGMT的预后意义，在62例患者中有35例（56.4%）检测到MGMT启动子高甲基化。26例（35.6%）肿瘤呈MGMT低阳性，24例（32.9%）呈MGMT中等阳性，23例（31.5%）呈MGMT高阳性。MGMT表达与MGMT启动子甲基化之间存在显著相关性（P < 0.001）。MGMT启动子甲基化和低MGMT表达均与较好的无进展生存期独立相关，但与较长的总生存期无关。然而，在亚组分析中，MGMT启动子甲基化与盐酸尼莫司汀（ACNU）治疗后接受替莫唑胺（TMZ）治疗的患者的总生存期延长显著相关，MGMT低表达和MGMT启动子甲基化均是胶质母细胞瘤患者肿瘤进展较慢的预测标志物。
The prognostic significance of O (6)-methylguanine DNA methyltransferase (MGMT) was evaluated by analysis of both MGMT promoter methylation and protein expression in a series of patients with newly diagnosed glioblastoma.Seventy-three patients with glioblastomas treated with alkylating agents were analyzed for MGMT expression by immunohistochemistry. Genomic DNA was isolated from frozen surgical specimens obtained from 62 of 73 patients. MGMT promoter methylation was determined by methylation-specific polymerase chain reaction. The prognostic significance of MGMT was evaluated together with other well-known prognostic factors.MGMT promoter hypermethylation was detected in 35 of 62 patients (56.4%). MGMT immunoreactivity was low in 26 (35.6%) tumors, moderate in 24 (32.9%), and high in 23 (31.5%). Significant correlation was observed between MGMT expression and MGMT promoter methylation (P < 0.001). Both MGMT promoter methylation and low MGMT expression were independently associated with better progression-free survival but not with longer overall survival. However, in the subgroup analysis, MGMT promoter hypermethylation was significantly associated with longer overall survival in patients treated with temozolomide (TMZ) after nimustine hydrochloride (ACNU) treatment.Low MGMT expression and MGMT promoter methylation are both predictive markers for slower tumor progression in patients with glioblastoma.