Detection of IDH1 mutation in human gliomas: comparison of immunohistochemistry and sequencing
Detection of IDH1 mutation in human gliomas: comparison of immunohistochemistry and sequencing
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DOI：
10.1007/s10014-011-0023-7
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发表时间：
2011-04-01
影响因子：
3.3
通讯作者：
Matsumura, Akira
中科院分区：
文献类型：
--
作者：
Takano, Shingo;Tian, Wei;Matsumura, Akira
异柠檬酸脱氢酶1（IDH 1）突变最近已被确定为星形细胞瘤，少突胶质细胞瘤和少突星形细胞瘤以及继发性胶质母细胞瘤的早期和频繁的遗传改变，而原发性胶质母细胞瘤很少含有IDH 1突变。此外，已经产生了识别IDH 1-R132 H（最常见的IDH 1突变）的特异性单克隆抗体IMAb-1。在Western印迹分析中，已经报道IMab-1与IDH 1-R132 H蛋白反应，但不与野生型IDH 1或其它IDH 1突变蛋白反应。然而，免疫组织化学使用IMAb-1的重要性尚未阐明。在这项研究中，我们使用49个胶质瘤样本比较了IMab-1免疫组化和直接DNA测序的结果。IMab-1检测到49个病例中的12个;然而，由于具有IDH 1-R132 H突变的肿瘤细胞的小群体，通过直接DNA测序仅发现9个病例是IDH 1-R132 H，表明IMab-1免疫组织化学可用于检测IDH 1-R132 H。我们对52例III级星形细胞瘤进行了免疫组化检测。与没有IDH 1突变的病例（野生型，10.4个月）相比，具有IDH 1突变的病例（86.7个月）的中位进展时间（TTP）显著更长（p < 0.01）。总之，抗IDH 1-R132 H特异性单克隆抗体IMab-1对于在免疫组织化学中检测IDH 1-R132 H和预测III级间变性星形细胞瘤的进展时间非常有用。因此，IMab-1很可能是有用的突变轴承胶质瘤的诊断和确定III级胶质瘤的治疗策略。
Isocitrate dehydrogenase 1 (IDH1) mutations have recently been identified as early and frequent genetic alterations in astrocytomas, oligodendrogliomas, and oligoastrocytomas, as well as secondary glioblastomas, whereas primary glioblastomas very rarely contain IDH1 mutations. Furthermore, a specific monoclonal antibody, IMab-1, which recognizes IDH1-R132H-the most frequent IDH1 mutation-has been generated. IMab-1 has been reported to react with the IDH1-R132H protein, but not the wild-type IDH1 or the other IDH1 mutant proteins in Western-blot analysis. However, the importance of immunohistochemistry using IMab-1 has not yet been elucidated. In this study, we compared the findings from IMab-1 immunohistochemistry and direct DNA sequencing using 49 glioma samples. IMab-1 detected 12 out of 49 cases; however, only nine cases were found to be IDH1-R132H by direct DNA sequencing because of a small population of IDH1-R132H mutation-possessing tumor cells, indicating that IMab-1 immunohistochemistry is useful for detecting IDH1-R132H. We conducted immunohistochemical detection in 52 cases of grade III astrocytomas. The median time to progression (TTP) was significantly longer in the cases with the IDH1 mutation (86.7 months) compared to the cases without the IDH1 mutation (wild type, 10.4 months) (p < 0.01). In conclusion, the anti-IDH1-R132H-specific monoclonal antibody IMab-1 is very useful for detecting IDH1-R132H in immunohistochemistry, and predicting the time to progression in grade III anaplastic astrocytomas. Therefore, IMab-1 is likely to be useful for the diagnosis of mutation-bearing gliomas and for determining the treatment strategy of grade III gliomas.