Mutation-specific IDH1 antibody differentiates oligodendrogliomas and oligoastrocytomas from other brain tumors with oligodendroglioma-like morphology.

Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-Universität Heidelberg, Germany.
Acta Neuropathologica (Impact Factor: 9.78). 11/2010; 121(2):241-52. DOI: 10.1007/s00401-010-0770-2
Source: PubMed

ABSTRACT 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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Cerebellar liponeurocytoma is a rare tumor that usually develops in adult patients, and is categorized as World Health Organization grade II. Because of the small number of reports on its radiological and pathological features, the disease remains poorly characterized. The current case involved a 59-year-old man with tumor in the upper cerebellar vermis. Preoperative positron emission tomography (PET) showed high uptake on (11)C-methionine PET, but low uptake on (18)F-fluorodeoxyglucose PET. These findings resemble those of central neurocytoma and oligodendroglioma, but are incompatible with other brain tumors. Subtotal tumor removal was performed by suboccipital craniotomy. Histopathological examinations showed sheets of small, isomorphic cells with round nuclei and clear cytoplasm, and focal vacuolated cells resembling adipose cells. On immunohistochemistry, tumor cells were positive for synaptophysin and NeuN. Vacuolated cells were immunoreactive for perilipin. Based on these findings, cerebellar liponeurocytoma was diagnosed. Genetic analyses revealed absences of both chromosome 1p/19q loss and isocitrate dehydrogenase 1 mutation, further ruling out oligodendroglioma. These radiological and genetic aspects of cerebellar liponeurocytoma, which are mostly in common with central neurocytoma, should prove helpful in differentiating this rare tumor from other tumors with similar morphology.
    Brain Tumor Pathology 12/2014; DOI:10.1007/s10014-014-0210-4 · 2.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Diffuse gliomas and secondary glioblastomas (GBMs) that develop from low-grade gliomas are a common and incurable class of brain tumor. Mutations in the metabolic enzyme glioblastomas (IDH1) represent a distinguishing feature of low-grade gliomas and secondary GBMs. IDH1 mutations are one of the most common and earliest detectable genetic alterations in low-grade diffuse gliomas, and evidence supports this mutation as a driver of gliomagenesis. Here, the authors highlight the biological consequences of IDH1 mutations in gliomas, the clinical and therapeutic/diagnostic implications, and the molecular subtypes of these tumors. They also explore, in brief, the non-IDH1-mutated gliomas, including primary GBMs, and the molecular subtypes and drivers of these tumors. A fundamental understanding of the diversity of GBMs and lower-grade gliomas will ultimately allow for more effective treatments and predictors of survival.
    Neurosurgical FOCUS 12/2014; 37(6):E13. DOI:10.3171/2014.9.FOCUS14505 · 2.14 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mutations of isocitrate dehydrogenase 1/2 (IDH1/2) have been reported in gliomas and other types of tumors, such as acute myeloid leukemias, cartilaginous tumors, intrahepatic cholangiocarcinomas, osteosarcomas, and giant cell tumors of bone. In gliomas, IDH mutations uniformly occur in the functionally critical arginine 132 residue (R132) of IDH1 and arginine 172 residue (R172) of IDH2. IDH1 and IDH2 catalyze the oxidative carboxylation of isocitrate to α-ketoglutarate (α-KG) in the cytosol and mitochondria, respectively. In contrast, mutated IDH1/2 proteins possess a neomorphic enzymatic function that changes α-KG into the oncometabolite, R(-)-2-hydroxyglutarate, resulting in genomic hypermethylation, histone methylation, genetic instability, and malignant transformation. To date, several monoclonal antibodies (mAbs) specific for IDH1/2 mutations such as anti-IDH1-R132H mAbs (clone H09, clone IMab-1, and clone HMab-1) or an anti-IDH1-R132S mAb (clone SMab-1) have been established. Furthermore, one of multi-specific mAbs, MsMab-1, recognizes IDH1 mutants (R132H, R132S, R132G) and IDH2 mutants (R172S, R172G), which are observed in gliomas. Another mAb, MsMab-2, recognizes IDH1-R132L and IDH2-R172M. These IDH1/2 mutation-specific mAbs are useful for the immunohistochemical determination of IDH1/2 mutation-bearing gliomas.
    Brain Tumor Pathology 10/2014; 32(1). DOI:10.1007/s10014-014-0202-4 · 2.28 Impact Factor