MGMT在恶性胶质瘤中的表达对替莫唑胺化疗预后的影响

Correlation of O^6-Methylguanine-DNA Methyltransferase with Prognosis of Malignant Glioblastoma Patients Treated with Temozolomide

目的通过检测肿瘤组织O6-甲基鸟嘌呤-DNA甲基转移酶(O6-methylguanine-DNA methyltrans-ferase,MGMT)的表达,探讨其对恶性胶质瘤替莫唑胺化疗预后的影响,以期为个体化化疗方案的选择提供临床依据。方法经病理学确诊为恶性胶质瘤患者60例,使用免疫组织化学方法检测肿瘤组织MGMT表达,根据表达情况分为MGMT阴性组和MGMT阳性组;所有患者均接受手术治疗及术后常规放射治疗和替莫唑胺化疗,并对其长期随访,进行无进展生存时间、实体肿瘤客观疗效和药物安全性的评定。结果肿瘤组织MGMT表达阴性者(-～±)为33例,MGMT表达阳性者(+～++)为27例;应用替莫唑胺化疗6个疗程末,MGMT阴性组客观有效率(CR+PR)为20/33,明显高于MGMT阳性组的5/27;MGMT阴性组平均无进展生存时间为(18±6.42)个月,明显长于MGMT阳性组的(9.0±1.91)个月,两组间差异具有统计学意义(P<0.01)。结论替莫唑胺化疗方案的疗效与MGMT在肿瘤组织中的表达程度密切相关,MGMT的检测对于指导恶性胶质瘤患者制定个体化化疗方案具有重要意义。

Objective To study MGMT expression level in tumor tissue and examine the effect of MGMT expression on the prognosis of malignant glioma after chemotherapy with temozolomide, to provide clinical evidence for the choice of individual chemotherapy. Methods Sixty patients with pathologically confirmed malignant gliomas were enrolled in this study. The glioma tissues were examined for MGMT protein expression by immunohistochemistry. The patients were divided into two groups according to MGMT expression level. All patients accepted surgical operation, routine radiotherapy and chemotherapy with temozolomide. The progression markers such as free survival time （PFS）, image based tumor response and drug safety were evaluated during the follow up period. Results The positive expression of MGMT （ - - ± ） was found in 33 patients, and negative expression （ ＋ - ＋ ＋ ） was found in 27 patients. After 6 treatment courses of TMZ, the objective curative rate in MGMT Negative group was 20/33 which was significantly higher than that in MGMT Positive group （5/27）. The average PFST in MGMT Negative group was 18 ± 6.42 months which was significantly longer than that in MGMT Positive group （9.0 ±1.91 months）. Conclusions Curative effect of temozolomide treatment is correlated closely with MGMT expression level in tumor tissue. The assessment of MGMT expression may help doctor to select chemotherapeutic schemes for patients with malignant glioma on individual basis.