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脑膜血管外皮细胞瘤:一项侧重于O(6)-甲基鸟嘌呤-DNA甲基转移酶(MGMT)启动子甲基化状态的临床病理研究

Meningeal hemangiopericytomas: a clinicopathological study with emphasis on MGMT (O(6) -methylguanine-DNA methyltransferase) promoter methylation status.

作者信息

Kakkar Aanchal, Kumar Anupam, Jha Prerana, Goyal Nishant, Mallick Supriya, Sharma Mehar Chand, Suri Ashish, Singh Manmohan, Kale Shashank S, Julka Pramod Kumar, Sarkar Chitra, Suri Vaishali

机构信息

Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.

出版信息

Neuropathology. 2014 Aug;34(4):333-42. doi: 10.1111/neup.12107. Epub 2014 Feb 12.

Abstract

Meningeal hemangiopericytomas (HPCs) are aggressive dural-based tumors, for which no prognostic or predictive marker has been identified. Gross total resection is treatment of choice, but not easily achieved; hence, alkylating agents like temozolomide (TMZ) are now being tried. O(6) -methylguanine-DNA methyltransferase (MGMT) promoter methylation has proven prognostic and predictive value in glioblastomas. This study evaluates MGMT promoter methylation in meningeal HPCs to determine its role in HPC oncogenesis and its association with patient outcome. Meningeal HPCs diagnosed between 2002 and 2011 were retrieved and clinicopathological features reviewed. MGMT promoter methylation status was assessed by methylation-specific polymerase chain reaction (MSP) and immunohistochemistry (IHC) for MGMT protein. HPCs accounted for 1.1% of all CNS tumors. Forty cases were analyzed; the majority were adults (mean age = 41.4 years). Seventy percent were primary and 30% were recurrent tumors; 60% were grade II and 40% were grade III. MGMT promoter methylation was identified in 45% of cases, including Grade II (54.2%) and Grade III (31.3%) (P = 0.203). Promoter methylation was significantly (P = 0.035) more frequent in primary (57.1%) than in recurrent (16.7%) tumors. No correlation was noted between MGMT promoter methylation by MSP and MGMT protein expression by IHC, or with progression-free survival. Thus, a significant proportion of HPCs demonstrate MGMT promoter methylation, suggesting possible susceptibility to TMZ. As promoter methylation is more frequent in primary tumors, TMZ may serve as a therapeutic option in residual primary tumors. Epigenetic inactivation of MGMT in HPCs necessitates the assessment of prognostic and predictive value of MGMT promoter methylation in HPCs in larger clinical trials.

摘要

脑膜血管外皮细胞瘤(HPCs)是一种侵袭性硬脑膜肿瘤,目前尚未发现其预后或预测标志物。肉眼全切是首选治疗方法,但不易实现;因此,现在正在尝试使用替莫唑胺(TMZ)等烷化剂。O(6)-甲基鸟嘌呤-DNA甲基转移酶(MGMT)启动子甲基化已被证明在胶质母细胞瘤中具有预后和预测价值。本研究评估脑膜HPCs中MGMT启动子甲基化情况,以确定其在HPC肿瘤发生中的作用及其与患者预后的关系。检索2002年至2011年间诊断的脑膜HPCs病例,并回顾其临床病理特征。通过甲基化特异性聚合酶链反应(MSP)和MGMT蛋白免疫组化(IHC)评估MGMT启动子甲基化状态。HPCs占所有中枢神经系统肿瘤的1.1%。分析了40例病例;大多数为成年人(平均年龄=41.4岁)。70%为原发性肿瘤,30%为复发性肿瘤;60%为Ⅱ级,40%为Ⅲ级。45%的病例中检测到MGMT启动子甲基化,其中Ⅱ级(54.2%)和Ⅲ级(31.3%)(P = 0.203)。原发性肿瘤(57.1%)中启动子甲基化显著高于复发性肿瘤(16.7%)(P = 0.035)。MSP检测的MGMT启动子甲基化与IHC检测的MGMT蛋白表达之间或与无进展生存期之间均未发现相关性。因此,相当一部分HPCs显示MGMT启动子甲基化,提示可能对TMZ敏感。由于原发性肿瘤中启动子甲基化更为常见,TMZ可作为残留原发性肿瘤的一种治疗选择。HPCs中MGMT的表观遗传失活需要在更大规模的临床试验中评估MGMT启动子甲基化在HPCs中的预后和预测价值。

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