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胶质肉瘤的临床病理和基因组特征。

Clinicopathologic and genomic features of gliosarcomas.

机构信息

Department of Pathology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea.

出版信息

J Neurooncol. 2012 May;107(3):643-50. doi: 10.1007/s11060-011-0790-3. Epub 2012 Jan 20.

Abstract

Gliosarcoma is a variant of glioblastoma (GBM) with both glial and mesenchymal differentiation. The genetic profile of gliosarcoma is similar to that of primary GBM, except for rare EGFR amplification. However, little is known about O6-methylguanine-DNA methyltransferase (MGMT) methylation and isocitrate dehydrogenase (IDH) 1/2 mutations in gliosarcomas. The objective of this study was to investigate the status of MGMT methylation and IDH1/2 mutations, and to determine the effect of current treatment options for 26 patients with gliosarcoma. Among 26 cases, 21 were primary gliosarcomas, four secondary gliosarcomas, and one radiation-induced gliosarcoma. MGMT methylation was detected in three cases (11.5%), of which one was found in primary gliosarcoma and two in secondary gliosarcoma. IDH1 mutation was found in two cases (7.7%), of which one was in secondary gliosarcoma and the other in primary gliosarcoma with MGMT methylation. A case of primary gliosarcoma with both IDH1 mutation and MGMT methylation had a focal oligodendroglial component. No IDH2 mutation was found. Patients who underwent gross total resection (GTR) during first surgery had better survival (mean overall survival 18.1 vs. 9.04 months; P = 0.0543). In multivariate analysis, GTR and/or gamma knife surgery at recurrence was the independent favorable prognostic factor (P = 0.0003). In conclusion, MGMT methylation and IDH1 mutation are rare events in gliosarcomas, and only aggressive and repetitive local control seems to be effective in treatment of gliosarcoma.

摘要

胶质肉瘤是一种具有胶质和间充质分化的胶质母细胞瘤(GBM)变体。除了罕见的 EGFR 扩增外,胶质肉瘤的遗传特征与原发性 GBM 相似。然而,关于胶质肉瘤中的 O6-甲基鸟嘌呤-DNA 甲基转移酶(MGMT)甲基化和异柠檬酸脱氢酶(IDH)1/2 突变知之甚少。本研究旨在探讨 MGMT 甲基化和 IDH1/2 突变的状态,并确定目前对 26 例胶质肉瘤患者的治疗选择的影响。在 26 例病例中,21 例为原发性胶质肉瘤,4 例为继发性胶质肉瘤,1 例为放射诱导的胶质肉瘤。在 3 例(11.5%)中检测到 MGMT 甲基化,其中 1 例在原发性胶质肉瘤中发现,2 例在继发性胶质肉瘤中发现。发现 IDH1 突变 2 例(7.7%),其中 1 例在继发性胶质肉瘤中,另 1 例在原发性胶质肉瘤中伴有 MGMT 甲基化。1 例原发性胶质肉瘤同时存在 IDH1 突变和 MGMT 甲基化,具有局灶性少突胶质细胞成分。未发现 IDH2 突变。在首次手术中进行大体全切除(GTR)的患者生存时间更长(总生存时间平均值分别为 18.1 个月和 9.04 个月;P=0.0543)。在多变量分析中,GTR 和/或复发时的伽玛刀手术是独立的有利预后因素(P=0.0003)。总之,MGMT 甲基化和 IDH1 突变在胶质肉瘤中罕见,只有积极和重复的局部控制似乎对胶质肉瘤的治疗有效。

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