Mutation-specific IDH1 antibody differentiates oligodendrogliomas and oligoastrocytomas from other brain tumors with oligodendroglioma-like morphology.
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.
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ABSTRACT: BACKGROUND: Significant progress has been made in the molecular diagnostic subtyping of brain tumors especially gliomas. Designing effective tailored therapy remains the cornerstone for delving into the molecular heterogeneity and classification of gliomas. More homogenous tumor populations may lead to more uniform tumor responses in particular molecular constellation. Recent decade has seen a surge of molecular markers of glioma which hold a promise and potential of being strong prognostic, predictive, and diagnostic markers. They are also extremely critical for the stratification of current clinical trails. METHOD: Review of the pertinent literature regarding the molecular markers of glioma was performed. Methods of detection of these markers and their clinical relevance are also discussed. RESULTS AND CONCLUSIONS: This review provides an update on progress and perspectives of these newest set of biomarkers which can also supplement and refine histological classification and serves as important prognostic and predictive markers; particularly relevant in this aspect are O(6)-methylguanine-DNA methyltransferase promoter methylation, IDH1 mutations, and codeletion of 1p/19q. BRAF fusion/mutations and EGFR amplification provide important clues diagnostically.Journal of Cancer Research and Clinical Oncology 10/2012; · 2.91 Impact Factor
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ABSTRACT: Neuronal differentiation of oligodendroglioma has been demonstrated by immunohistochemical and ultrastructural examinations in recent studies. However, oligodendrogliomas displaying a complete neurocytic morphology or even gangliocytic differentiation are rare. We describe a case of anaplastic oligodendroglioma that was characterized by the presence of ganglion cells in a 40-year-old-male. Histologically, the tumor was mainly composed of classical oligodendroglioma cells. The most exceptional finding of this tumor was the presence of ganglion cells and intermediate-sized ganglioid cells. Immunohistochemical analysis revealed that these cells were positive for Olig2 and negative for glial fibrillary acid protein (GFAP). Synaptophysin and microtubule-associated protein 2 (MAP2) were mainly detected in the ganglion cells. Fluorescence in situ hybridization analysis (FISH) revealed the deletion of the 1p and 19q chromosome arms in both the oligodendroglioma cells and ganglion cells. The R132H mutated isocitrate dehydrogenase 1 (IDH1) protein was detected by immunohistochemistry and direct DNA sequencing. The morphological, immunohistochemical, and genetic features of the tumor suggested a diagnosis of anaplastic oligodendroglioma, and this tumor was considered to be a rare form of oligodendroglioma displaying ganglioglioma-like maturation. FISH and mutant IDH1 examinations are useful diagnostic tools for the differential diagnosis of this tumor, i.e., ganglioglioma with anaplastic oligodendroglial features.Brain Tumor Pathology 01/2012; · 1.58 Impact Factor
- Acta Neuropathologica 07/2012; 124(3):449-51. · 9.73 Impact Factor