启动子超甲基化和免疫组织化学表达的 O(6)-甲基鸟嘌呤 DNA 甲基转移酶与胶质母细胞瘤患者的无进展生存期相关。
O(6)-Methylguanine DNA methyltransferase determined by promoter hypermethylation and immunohistochemical expression is correlated with progression-free survival in patients with glioblastoma.
机构信息
Department of Neurosurgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
出版信息
Int J Clin Oncol. 2010 Aug;15(4):352-8. doi: 10.1007/s10147-010-0065-6. Epub 2010 Mar 16.
OBJECTIVE
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
Low MGMT expression and MGMT promoter methylation are both predictive markers for slower tumor progression in patients with glioblastoma.
目的
通过分析新诊断的胶质母细胞瘤患者中 O(6)-甲基鸟嘌呤 DNA 甲基转移酶 (MGMT) 的启动子甲基化和蛋白表达，评估其预后意义。
方法
对 73 例接受烷化剂治疗的胶质母细胞瘤患者进行免疫组化分析，检测 MGMT 表达。从 73 例患者中的 62 例冷冻手术标本中提取基因组 DNA。采用甲基化特异性聚合酶链反应检测 MGMT 启动子甲基化。将 MGMT 的预后意义与其他已知的预后因素一起进行评估。
结果
在 62 例患者中检测到 35 例（56.4%）MGMT 启动子甲基化。26 例（35.6%）肿瘤的 MGMT 免疫反应性低，24 例（32.9%）中度，23 例（31.5%）高。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 表达均与无进展生存期延长独立相关，但与总生存期延长无关。然而，在亚组分析中，MGMT 启动子高甲基化与接受替莫唑胺（TMZ）治疗的患者的总生存期延长显著相关。
结论
低 MGMT 表达和 MGMT 启动子甲基化都是胶质母细胞瘤患者肿瘤进展缓慢的预测标志物。
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