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病理类型、IDH-1突变和MGMT启动子甲基化状态与间变性胶质瘤假性进展的相关性

The association of pathological type、IDH-1 mutations and MGMT promoter methylation status on "pseudo-progress" of anaplastic gliomas

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【作者】 李宏陆云涛漆松涛俞磊欧阳辉刘亚伟

【Author】 LI Hong1,LU Yuntao1,QI Songtao1,YU Lei1,OUYANG Hui1,LIU Yawei2(1.Department of Neurosurgery,the Affiliated Nangfang Hospital,Southern Medical University,Guangzhou,510515,China; 2.Department of Pahtophysiology and Key Laboratory of Functional Proteomics of Guangdong Province, Souhtern Medical University,Guangzhou,510515,China)

【机构】 南方医科大学南方医院神经外科南方医科大学病理生理学教研室和广东省功能蛋白质组重点实验室

【摘要】 目的:明确间变性胶质瘤(Anaplastic glioma,AG)组织中病理类型、IDH-1基因突变以及MGMT启动子甲基化与患者综合治疗后发生假性进展(Pseudoprogression,PsPD)之间的相互关系。方法:对47例间变性胶质瘤标本采用基因片段测序的方法检测异柠檬酸脱氢酶(IDH-1)突变和MGMT启动子甲基化状态情况。对所有病例进行临床随访,结合肿瘤的病理类型,探讨其对术后PsPD发生的提示作用。结果:47例AG患者中有24例出现早期进展(6个月内)。9例PsPD中IDH-1突变和MGMT启动子甲基化分别是6例和7例;另15例真性复发患者IDH-1突变和MGMT启动子甲基化分别是3例和5例,IDH-1突变对PsPD检出率与MGMT启动子甲基化相比,无明显差异(2<0.02,P>0.9);PsPD中含少突胶质细胞病理成分的4例病例,包括3例间变性少突胶质细胞瘤(AO)和1例间变性少突显形细胞瘤(AOA),全部发生IDH-1突变,另5例间变性显形细胞瘤(AA)中有2例发生IDH-1突变,IDH-1突变对PsPD检出率与病理类型中含少突胶质细胞成分相比,无明显差异(2=0.5,P>0.5)。结论:病理类型中含有少突胶质细胞成分、存在IDH-1突变和MGMT启动子甲基化可以作为间变性胶质瘤中预测PsPD的可靠客观预计指标,有利于鉴别肿瘤PsPD和真性复发。

【Abstract】 Aim:To identify the relationship between Pathological type,IDH mutation,MGMT promoter methylation in clinical samples of anaplastic gliomas(AG) with Pseudoprogression(PsPD) in patients received comprehensive treatment.Methods: DNA direct sequencing was used to detect IDH-1 mutation and MGMT promoter methylation status of the 47 clinical samples of AG.Clinical data of all patients with AG treated with surgery followed by radiotherapy plus(or not) concomitant temozolomide(TMZ) were followed up.IDH mutation and MGMT promoter methylation were analyzed statistically combined with pathological type of tumor to identify the predictive role of them on postoperative PsPD.Results: Twenty-four of 47 cases were considered as radiological progression(RP).The role of IDH-1 mutant、MGMT promoter methylation and pathological type are consistent in predicting PsPD.Among of them,nine were PsPD and the other 15 cases were truly progression(TP).There were 6 cases of IDH-1 mutation and 7 cases of MGMT promoter methylation in 9 cases of PsPD but 3 case of IDH-1 mutation and 5 cases of MGMT promoter methylation in 15 cases of TP.There is no significant difference between IDH-1 mutation and MGMT promoter methylation in detection rate of "PsPD"(X2<0.02,P>0.9);In PsPD,4 cases(three AO and one AOA) containing Oligodendrocyte pathology ingredients all occurred IDH-1 mutation and only 2 in 5 case of AA occurred IDH-1 mutation.There is no significant difference between IDH-1 mutation and pathological type containing oligodendrocyte ingredients in detection rate of "PsPD"(X2 =0.5,0.5<P<0.75).Conclusion:The pathological type contains oligodendrocytes ingredients,IDH-1 mutation and MGMT promoter methylation can be reliable objective indicator of predicting PsPD in anaplastic glioma and favor differentiating tumor PsPD with recurrence.

【基金】 国家自然科学基金青年科学基金项目(81101921)
  • 【文献出处】 暨南大学学报(自然科学与医学版) ,Journal of Jinan University(Natural Science & Medicine Edition) , 编辑部邮箱 ,2013年02期
  • 【分类号】R739.4
  • 【被引频次】4
  • 【下载频次】338
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