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  • antibody  (2)
  • BRAF(V600E) MUTATION  (1)
  • 1
    Keywords: Germany ; DIAGNOSIS ; TOOL ; PROTEIN ; DIFFERENTIATION ; antibody ; GLIOMAS ; oligodendroglioma ; 19Q ; IMMUNOREACTIVITY ; IDH1 ; CODON 132 MUTATION ; ISOCITRATE DEHYDROGENASE ; R132H ; CHROMOSOMES 1P ; Clear cell ; EXTRAVENTRICULAR NEUROCYTOMA ; NEUROEPITHELIAL TUMORS ; PEDIATRIC OLIGODENDROGLIOMAS
    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.
    Type of Publication: Journal article published
    PubMed ID: 21069360
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  • 2
    Keywords: brain ; CELLS ; INVASION ; TUMOR-CELLS ; TUMORS ; antibodies ; antibody ; CENTRAL-NERVOUS-SYSTEM ; IDH2 MUTATIONS
    Abstract: Objective: To analyze infiltration patterns of IDH1 mutant diffuse gliomas into the brain by identification of single tumor cells applying an antibody specific to mutant IDH1 R132H protein. Design: Immunohistochemical analysis. Setting: University hospital. Patients: Whole-brain and hemisphere sections of 4 patients diagnosed with diffuse glioma. Results: Tumor cells were identified in areas that appeared inconspicuous macroscopically and at histological analysis with respect to cellularity, cellular pleomorphism, or mitotic activity in all cases. Conclusion: Detection of single tumor cells throughout the brain demonstrates diffuse glioma to represent systemic brain disease
    Type of Publication: Journal article published
    PubMed ID: 22158715
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  • 3
    Keywords: MONOCLONAL-ANTIBODY ; DELETION ; LESIONS ; immunohistochemistry ; LOW-GRADE GLIOMAS ; THYROID-CANCER ; CASE SERIES ; V600E mutation ; BRAF(V600E) MUTATION ; DYSEMBRYOPLASTIC NEUROEPITHELIAL TUMORS
    Abstract: BRAF V600E mutation and homozygous deletion of CDKN2A (p16) are frequent molecular alterations in pleomorphic xanthoastrocytomas (PXAs). We investigated 49 PXAs for clinical, histological and immunohistochemical characteristics related to BRAF mutation status. BRAF mutation was detected by immunohistochemical assay and DNA sequencing in 38/49 (78%) tumors. All but one PXA located in the temporal lobe harbored a BRAF V600E mutation (23/24; 96%) compared with 10/19 nontemporal PXAs (53%; P = 0.0009). Histological and immunohistochemical analysis demonstrated increased reticulin deposition (76% vs. 27%; P = 0.003) and a more frequent expression of CD34 in BRAF-mutant PXAs (76% vs. 27%; P = 0.003). We further investigated the utility of combined BRAF V600E (VE1) and p16 analysis by immunohistochemistry to distinguish PXAs from relevant histological mimics like giant-cell glioblastoma. Among PXAs, 38/49 (78%) were VE1-positive, and 30/49 (61%) had a loss of p16 expression. The combined features (VE1 positivity/p16 loss) were observed in 25/49 PXAs (51%) but were not observed in giant-cell glioblastoma (VE1 0/28, p16 loss 14/28). We demonstrate that temporal location, reticulin deposition and CD34 expression are associated with BRAF mutation in PXA. Combined VE1 positivity and p16 loss represents a frequent immunoprofile of PXA and may therefore constitute an additional diagnostic tool for its differential diagnosis.
    Type of Publication: Journal article published
    PubMed ID: 24345274
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