Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-Universität Heidelberg, Germany.
Acta Neuropathol. 2011 Feb;121(2):241-52. doi: 10.1007/s00401-010-0770-2. Epub 2010 Nov 11.
Isocitrate dehydrogenase 1 (IDH1) mutations are frequent in astrocytomas, oligoastrocytomas and oligodendrogliomas. We previously reported the generation of a mutation-specific antibody that specifically detects R132H mutated IDH1 protein (clone H09). Here, we investigate the feasibility of H09 immunohistochemistry to differentiate between oligodendrogliomas/oligoastrocytomas and other tumors with similar morphology. A total of 274 brain tumors presenting with focal or extensive clear cell morphology were investigated. High numbers of H09-positive cases were observed in adult grade II oligodendrogliomas (67 of 74, 91%), grade III oligodendrogliomas (65 of 69, 94%), grade II oligoastrocytomas (11 of 14, 79%) and grade III oligoastrocytomas (10 of 11, 91%). All cases of pediatric oligodendrogliomas (n = 7), neurocytomas (n = 41, 35 central, 4 extraventricular, 2 cerebellar liponeurocytomas), dysembryoplastic neuroepithelial tumors (n = 21), clear cell ependymomas (n = 8), clear cell meningiomas (n = 9) as well as 12 primary glioblastomas with oligodendroglial differentiation and 5 pilocytic astrocytomas with oligodendroglial-like differentiation were negative for H09 immunohistochemistry. Three oligodendrogliomas with neurocytic differentiation had evidence of IDH1/IDH2 mutations either by H09 immunohistochemistry or direct sequencing. We conclude that in tumors with an oligodendroglioma-like morphology, binding of H09 is highly specific for oligodendrogliomas or oligoastrocytomas and substantially helps in the discrimination from other clear cell tumors. Negative H09 immunohistochemistry of an adult oligodendroglioma or oligoastrocytoma should prompt the consideration of other clear cell neoplasms. Further, our observations firmly assign oligodendrogliomas with neurocytic differentiation to the group of oligodendrogliomas and demonstrate that H09 is especially helpful for the difficult discrimination of such lesions from extraventricular neurocytomas.
异柠檬酸脱氢酶 1（IDH1）突变在星形细胞瘤、少突星形细胞瘤和少突胶质细胞瘤中很常见。我们之前报道了一种突变特异性抗体的产生，该抗体特异性检测 R132H 突变的 IDH1 蛋白（克隆 H09）。在这里，我们研究了 H09 免疫组织化学在区分少突胶质细胞瘤/少突星形细胞瘤和其他具有相似形态的肿瘤方面的可行性。共研究了 274 例具有局灶性或广泛透明细胞形态的脑肿瘤。在成人 2 级少突胶质细胞瘤（74 例中的 67 例，91%）、3 级少突胶质细胞瘤（69 例中的 65 例，94%）、2 级少突星形细胞瘤（14 例中的 11 例，79%）和 3 级少突星形细胞瘤（11 例中的 10 例，91%）中观察到大量 H09 阳性病例。所有儿童少突胶质细胞瘤（n=7）、神经细胞瘤（n=41，35 例中枢，4 例脑室外，2 例小脑脂肪神经细胞瘤）、发育不良性神经上皮肿瘤（n=21）、透明细胞室管膜瘤（n=8）、透明细胞脑膜瘤（n=9）以及 12 例伴少突胶质分化的原发性胶质母细胞瘤和 5 例伴少突胶质样分化的毛细胞星形细胞瘤均为 H09 免疫组织化学阴性。3 例伴有神经细胞分化的少突胶质细胞瘤通过 H09 免疫组织化学或直接测序证实存在 IDH1/IDH2 突变。我们的结论是，在具有少突胶质细胞瘤样形态的肿瘤中，H09 的结合高度特异性地用于少突胶质细胞瘤或少突星形细胞瘤，并大大有助于与其他透明细胞肿瘤的鉴别。成人少突胶质细胞瘤或少突星形细胞瘤的 H09 免疫组织化学阴性应促使考虑其他透明细胞肿瘤。此外，我们的观察结果明确将具有神经细胞分化的少突胶质细胞瘤归入少突胶质细胞瘤组，并证明 H09 特别有助于从脑室外神经细胞瘤中难以区分这些病变。
