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免疫组织化学检测 IDH1 突变、p53 和连接蛋白作为神经胶质瘤的预后因素。

Immunohistochemical detection of IDH1 mutation, p53, and internexin as prognostic factors of glial tumors.

机构信息

Department of Neurological Surgery, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennoudai, 305-8575, Ibaraki, Tsukuba, Japan.

出版信息

J Neurooncol. 2012 Jul;108(3):361-73. doi: 10.1007/s11060-012-0837-0. Epub 2012 Mar 7.

Abstract

Isocitrate dehydrogenase 1 (IDH1) mutations, which are early and frequent genetic alterations in astrocytomas, oligodendrogliomas, oligoastrocytomas, and secondary glioblastomas, are specific to arginine 132 (R132). Recently, we established monoclonal antibodies (mAbs) against IDH1 mutations: anti-IDH1-R132H and anti-IDH1-R132S. However, the importance of immunohistochemistry using the combination of those mAbs has not been elucidated. For this study, 164 cases of glioma were evaluated immunohistochemically for IDH1 mutations (R132H and R132S) using anti-IDH1 mAbs (HMab-1 and SMab-1). IDH1 mutation was detected, respectively, in 9.7%, 63.6%, 51.7%, and 77.8% of primary grade IV, secondary grade IV, grade III, and grade II gliomas. For each grade of glioma, prognostic factors for progression-free survival and overall survival were evaluated using clinical and pathological parameters in addition to IDH1 immunohistochemistry. IDH1 mutation, p53 overexpression, and internexin expression, as evaluated using immunohistochemistry with clinical parameters such as degree of surgical removal and preoperative Karnofsky Performance Status (KPS), might be of greater prognostic significance than histological grading alone in grade III as well as IDH1 mutation in grade IV gliomas.

摘要

异柠檬酸脱氢酶 1(IDH1)突变是星形细胞瘤、少突胶质瘤、少突星形细胞瘤和继发性胶质母细胞瘤中早期且频繁发生的遗传改变,其特异性在于精氨酸 132(R132)。最近,我们建立了针对 IDH1 突变的单克隆抗体(mAbs):抗 IDH1-R132H 和抗 IDH1-R132S。然而,使用这些 mAbs 组合进行免疫组织化学的重要性尚未阐明。在这项研究中,使用抗 IDH1 mAbs(HMab-1 和 SMab-1)对 164 例胶质瘤进行了 IDH1 突变(R132H 和 R132S)的免疫组织化学评估。原发性 IV 级、继发性 IV 级、III 级和 II 级胶质瘤中分别检测到 IDH1 突变,分别为 9.7%、63.6%、51.7%和 77.8%。对于每个级别的胶质瘤,除了 IDH1 免疫组织化学外,还使用临床和病理参数评估了无进展生存期和总生存期的预后因素。IDH1 突变、p53 过表达和神经丝中间丝表达,通过免疫组织化学与手术切除程度和术前卡诺夫斯基表现状态(KPS)等临床参数评估,在 III 级胶质瘤中可能比单独组织学分级更具预后意义,而在 IV 级胶质瘤中 IDH1 突变也是如此。

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