脑胶质瘤分子标志物IDH1R132突变、MGMT和Ki-67与病理分级及预后关系的研究

Study on the relationship between molecular markers IDH1R132 mutation,MGMT and Ki-67 and pathologic grade and prognosis of brain gliomas

目的联合检测脑胶质瘤中异柠檬酸脱氢酶1R132位点核苷酸突变(IDH1R132突变)、O^6-甲基鸟嘌呤-DNA-甲基转移酶(MGMT)和Ki-67蛋白的表达,探讨其表达与胶质瘤病理分级的相关性及对预后的影响。方法收集脑胶质瘤病理标本135例,采用免疫组织化学方法检测病理标本中IDH1R132突变、MGMT和Ki-67蛋白的表达情况,并对此部分患者进行长期随访,从而分析这3种分子标志物的表达与病理分级及预后的相关性。结果 135例脑胶质瘤标本中IDH1R132突变总阳性表达率为31.1%(42/135),Ⅱ级、Ⅲ级及Ⅳ级脑胶质瘤标本中IDH1R132突变阳性表达率分别为49.1%、22.2%、11.8%,三者间表达差异有统计学意义(P<0.01);IDH1R132突变阳性表达者中位生存时间明显高于阴性表达者,分别为27个月和13个月(P<0.01)。MGMT总体阳性表达率为42.2%,不同级别的胶质瘤之间MGMT阳性表达率差异无统计学意义;MGMT阳性表达者中位生存时间(12个月)低于阴性者(23个月)(P<0.01)。所有患者Ki-67呈阳性表达,Ⅱ-Ⅳ级胶质瘤中Ki-67的表达率呈上升趋势,不同级别的胶质瘤之间Ki-67阳性表达程度差异有统计学意义(P<0.001);Ki-67表达程度与患者中位生存时间无显著差异。结论 IDH1R132突变、Ki-67的表达水平与肿瘤的恶性程度密切相关,IDH1R132突变、MGMT在不同级别胶质瘤的预后评价中具有重要意义,可作为预后的独立预测指标。

Objective To investigate the expression of IDH1 R132 mutation, MGMT and Ki-67 protein in glioma, and explore the correlation between the expression and the pathological grading and prognosis of gliomas. Methods A total of 135 glioma patients were collected. The expressions of IDH1R132, MGMT and Ki-67 in pathological specimens were detected by immunohistochemistry . We analyzed the relationship between the expression of three molecular markers and the pathological grading patients, Results The total positive expression and prognosis of gliomas through long-term follow-up of this part of rate of IDH1R132 mutation was 31.1% （42/135） in 135 cases of brain glioma specimens, while in grade Ⅱ , Ⅲ and Ⅳ gliomas were 49. 1% , 22.2% and 11.8% respectively. As a result, there were statistically significant differences among different grades of gliomas （P 〈 0. 01 ）. The median survival time of IDHI R132 mutation was significantly higher than that of negative expression, 27 months and 13 months respectively （P 〈 0. 01 ）. The overall positive expression rate of MGMT was 42.2%, and there was no sta- tistically significant difference between different grades of gliomas （P 〉 0. 05 ）. The median survival time of MGMT positive expression was 23 months, which was lower than that of the negative group for 12 months （P 〈 0.01 ）. Ki- 67 expression was positive in all patients, and the expression level of Ki-67 was increased in the grade Ⅱ - Ⅲ glio- mas. Though there were statistically significant differences in Ki-67 expression among different grades of gliomas （ P 〈 0. 001 ）, the expression level of Ki-67 had no relationship with median survival time of the patients （P 〉 0. 05 ）. Conclusion The expression levels of IDH1R132 mutation and Ki-67 are closely related to the malignant degree of brain gliomas, while IDH1 R132 mutation and MGMT have important significance in the evaluation of the prognosis of gliomas at different levels. In conclusion, they can be used as independent predictors of prognosis in glioma pa- tients.