THE CORRELATION AND PROGNOSTIC SIGNIFICANCE OF MGMT PROMOTER METHYLATION AND MGMT PROTEIN IN GLIOBLASTOMAS
THE CORRELATION AND PROGNOSTIC SIGNIFICANCE OF MGMT PROMOTER METHYLATION AND MGMT PROTEIN IN GLIOBLASTOMAS
复制标题
DOI：
10.1227/01.neu.0000357325.90347.a1
复制
发表时间：
2009-11-01
期刊：
影响因子：
4.8
通讯作者：
Chae, Hong-Jae
中科院分区：
文献类型：
--
作者：
Cao, Van Thang;Lung, Tae-Young;Chae, Hong-Jae
目的：本研究的目的是评估胶质母细胞瘤患者MGMT启动子甲基化和蛋白表达的相关性和预后意义。方法：2000年10月至2008年6月，83例胶质母细胞瘤患者接受手术，随后接受放疗和替莫唑胺化疗。采用甲基化特异性聚合酶链反应（MSP）和免疫组织化学染色方法研究MGMT甲基化与MGMT表达的相关性。为了分析MGMT甲基化和MGMT表达之间的相关性，根据位置，从12名患者的肿瘤内的37个不同部位获得活检组织。年龄、性别、Karnofsky行为量表状态、切除程度、化疗方法、MGMT启动子甲基化和蛋白表达作为预后因素进行分析。结果：总的中位生存期为15.8个月（范围12.6-19.1个月）。12例患者不同部位的MSP结果相同。在50%的患者中观察到MSP和免疫组化染色之间的相关性。在73例患者中，44例MGMT启动子甲基化患者中70.5%的患者MGMT表达阴性，29例非甲基化患者中55.2%的患者MGMT表达阳性。多变量分析显示，切除程度（P = 0.001）和MGMT启动子甲基化和阴性MGMT表达（中位生存期，20.06个月; P = 0.006）的组合与较长的生存期显着相关。结论：我们报告使用MSP结合免疫组化染色作为预后因素的可行性。本研究的结果表明，MGMT启动子甲基化结合MGMT表达阴性可能是胶质母细胞瘤患者的一个良好的预后因素。
OBJECTIVE: The aim of this study was to evaluate the correlation and prognostic significance of MGMT promoter methylation and protein expression in patients with glioblastoma.METHODS: Eighty-three patients with glioblastoma underwent surgery followed by radiotherapy and temozolomide chemotherapy between October 2000 and June 2008. To investigate the correlation between MGMT methylation and MGMT expression, methylation-specific polymerase chain reaction (MSP) and immunohistochemical staining was performed. To analyze the correlation between MGMT methylation and MGMT expression according to location, biopsies were obtained from 37 different sites within the tumors in 12 patients. Age, sex, Karnofsky Performance Scale status, extent of removal, chemotherapeutic methods, and MGMT promoter methylation and protein expression were analyzed as prognostic factors.RESULTS: The total median survival was 15.8 months (range, 12.6-19.1 months). The results of MSP were the same at various sites in 12 patients. A correlation between MSP and immunohistochemical staining was observed in 50% of the patients. In 73 patients, negative MGMT expression was detected in 70.5% of 44 patients with MGMT promoter methylation, and positive expression was observed in 55.2% of the 29 patients with unmethylated promoters. Multivariate analysis revealed that the extent of removal (P = 0.001) and the combination of MGMT promoter methylation and negative MGMT expression (median survival, 20.06 months; P = 0.006) were significantly associated with longer survival.CONCLUSION: We report the feasibility of using MSP combined with immunohistochemical staining as a prognostic factor. The results of the present study suggest that MGMT promoter methylation in combination with negative MGMT expression might be a good prognostic factor in patients with glioblastoma.