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: In an attempt to characterize differentiation in oligodendrogliomas, 39 cases were examined immunohistochemically with 5 neuronal markers, synaptophysin, neuron- specific enolase, neurofilament proteins, protein gene product (PGP) 9.5, and micro tubule-associated protein 2 (MAP2), in addition to glial fibrillary acidic protein (GFAP). Positive immunolabeling was obtained for neuron-specific enolose in 29 cases (74%), synaptophysin in 21 cases (54%), PGP 9.5 in 33 cases (85%), and MAP2 in 23 cases (59%). All cases were negative for neurofilament, and 90% stained for GFAP. Eight cases were further studied ultrastructurally, and in five cases features of neuronal differentiation were identified in some of the typical neoplastic oligodendro cytes—small neuritic cellular processes with microtubules and focal synapse-like junc tions, as well as sparse neurosecretory granules. It was concluded that, both immuno histochemically and ultrastructurally, oligodendrogliomas may exhibit features of neuronal differentiation. These previously unreported features of oligodendrogliomas call into question conventional immunohistochemical and electron microscopic crite ria used in distinguishing oligodendrogliomas from tumors showing similar histologic appearance, especially central neurocytomas and dysembryoplastic neuroepithelial tu mors. Int J Surg Pathol 2(1):47-56 1994International Journal of Surgical Pathology - INT J SURG PATHOL. 01/1994; 2(1):47-55.
- Brain Pathology - BRAIN PATHOL. 01/2006; 16(1):89-90.
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ABSTRACT: Complex and variable morphological phenotypes pose a major challenge to the histopathological classification of neuroepithelial tumors. This applies in particular for low-grade gliomas and glio-neuronal tumors. Recently, we and others have identified microtubule-associated protein-2 (MAP2) as an immunohistochemical marker expressed in the majority of glial tumors. Characteristic cell morphologies can be recognized by MAP2 immunoreactivity in different glioma entities, i.e., process sparse oligodendroglial versus densely ramified astrocytic elements. Here, we describe MAP2-immunoreactivity patterns in a large series of various neuroepithelial tumors and related neoplasms (n = 960). Immunohistochemical analysis led to the following conclusions: (1) specific pattern of MAP2-positive tumor cells can be identified in 95% of glial neoplasms; (2) ependymal tumors do not express MAP2 in their rosette-forming cell component; (3) tumors of the pineal gland as well as malignant embryonic tumors are also characterized by abundant MAP2 immunoreactivity; (4) virtually no MAP2 expression can be observed in the neoplastic glial component of glio-neuronal tumors, i.e. gangliogliomas; (5) malignant glial tumor variants (WHO grade III or IV) exhibit different and less specific MAP2 staining patterns compared to their benign counterparts (WHO grade I or II); (6) with the exception of melanomas and small cell lung cancers, MAP2 expression is very rare in metastatic and non-neuroepithelial tumors; (7) glial MAP2 expression was not detected in 56 non-neoplastic lesions. These data point towards MAP2 as valuable diagnostic tool for pattern recognition and differential diagnosis of low-grade neuroepithelial tumors.Acta Neuropathologica 09/2004; 108(2):89-96. · 9.73 Impact Factor