异柠檬酸脱氢酶1（IDH1）状态在高级别丘脑胶质瘤和浅表性胶质瘤之间存在显著差异。

IDH1 status is significantly different between high-grade thalamic and superficial gliomas.

作者信息

Zuo Mingrong, Li Mao, Chen Ni, Yu Tianping, Kong Bing, Liang Ruofei, Wang Xiang, Mao Qing, Liu Yanhui

机构信息

Department of Neurosurgery, Sichuan University, West China Hospital, Chengdu, Sichuan, China.

Department of Pathology, Sichuan University, West China Hospital, Chengdu, Sichuan, China.

出版信息

Cancer Biomark. 2017 Aug 23;20(2):183-189. doi: 10.3233/CBM-170175.

DOI:10.3233/CBM-170175

PMID:28869450

Abstract

BACKGROUND

While major progress has been made in diagnosis and treatment of gliomas based on molecules, molecular features of thalamic glioma have rarely been reported till now.

OBJECTIVE

IDH1 mutation is important for prognosis of gliomas and represents a distinctive category of glioma. We intended to survey specific molecular abnormalities in high-grade thalamic gliomas (WHO III-IV).

METHODS

We collected data of 50 and 93 newly diagnosed high-grade thalamic and superficial glioma patients respectively and conducted a comparative analysis of molecular characteristics between them. We analyzed expressions of molecules as follow: IDH1/2, P53, Ki-67, ATRX, PTEN, MMP9 and MGMT by Immunohistochemistry (IHC). Direct gene sequencing was performed to test the IDH1(R 132H) mutation.

RESULTS

We found a significant difference of IDH1 mutation between those high-grade gliomas, with 92% (46/50) of the thalamic tumors and 71% (66/93) of the superficial gliomas showing IDH1 wild-type (p= 0.004). It also showed that IDH1 mutation in superficial glioblastomas 18.6% (13/70) occurred more than thalamic glioblastomas 2.6% (1/39) (p= 0.017). As to high-grade superficial gliomas, there were 26 patients with IDH1 mutation, which contained 7, 13, and 6 high, moderate and low Ki-67 expression gliomas, respectively. The IDH1 wild-type group (62 patients), was composed of 29, 30, and 3 high, moderate and low Ki-67 expression gliomas, respectively. There was a significant distinction between the IDH1 mutation and Ki-67 expressions (p= 0.024). We also noted that the occurrence of low Ki-67 expressions 23.1% (6/26) in IDH1 mutation group was outnumbered than IDH1 wild-type group 4.8% (3/62) (p= 0.018). In addition, we found PTEN negative correlated with MMP9 negative in thalamic high-grade gliomas, whereas no such difference was found in superficial gliomas (p= 0.016).

CONCLUSION

The rare occurrence of IDH1 mutant high-grade thalamic gliomas strongly suggested that the high-grade thalamic glioma is another distinct tumor entity as compared to the high-grade superficial gliomas.

摘要

背景

虽然基于分子的胶质瘤诊断和治疗已取得重大进展，但丘脑胶质瘤的分子特征至今鲜有报道。

目的

异柠檬酸脱氢酶1（IDH1）突变对胶质瘤预后具有重要意义，代表了一种独特的胶质瘤类别。我们旨在调查高级别丘脑胶质瘤（世界卫生组织III - IV级）的特定分子异常情况。

方法

我们分别收集了50例新诊断的高级别丘脑胶质瘤患者和93例新诊断的高级别浅表性胶质瘤患者的数据，并对两者的分子特征进行了对比分析。我们通过免疫组织化学（IHC）分析了以下分子的表达：IDH1/2、P53、Ki-67、ATRX、PTEN、基质金属蛋白酶9（MMP9）和O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）。进行直接基因测序以检测IDH1（R132H）突变。

结果

我们发现这些高级别胶质瘤之间IDH1突变存在显著差异，丘脑肿瘤中有92%（46/50）显示IDH1野生型，浅表性胶质瘤中有71%（66/93）显示IDH1野生型（p = 0.004）。还显示浅表性胶质母细胞瘤中IDH1突变发生率为18.6%（13/70），高于丘脑胶质母细胞瘤的2.6%（1/39）（p =

0.017）。对于高级别浅表性胶质瘤，有26例患者存在IDH1突变，其中分别有7例、13例和6例高、中、低Ki-67表达的胶质瘤。IDH1野生型组（62例患者）分别由29例、30例和3例高、中、低Ki-67表达的胶质瘤组成。IDH1突变与Ki-67表达之间存在显著差异（p = 0.024）。我们还注意到IDH1突变组中低Ki-67表达的发生率为23.1%（6/26），高于IDH1野生型组的4.8%（3/62）（p = 0.018）。此外，我们发现丘脑高级别胶质瘤中PTEN与MMP9呈负相关，而浅表性胶质瘤中未发现这种差异（p = 0.016）。