Skip to main content
Top
Published in: Acta Neuropathologica 2/2011

01-02-2011 | Original Paper

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

Authors: David Capper, David Reuss, Jens Schittenhelm, Christian Hartmann, Juliane Bremer, Felix Sahm, Patrick N. Harter, Astrid Jeibmann, Andreas von Deimling

Published in: Acta Neuropathologica | Issue 2/2011

Login to get access

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.
Literature
1.
go back to reference Balss J, Meyer J, Mueller W et al (2008) Analysis of the IDH1 codon 132 mutation in brain tumors. Acta Neuropathol 116:597–602CrossRefPubMed Balss J, Meyer J, Mueller W et al (2008) Analysis of the IDH1 codon 132 mutation in brain tumors. Acta Neuropathol 116:597–602CrossRefPubMed
2.
go back to reference Bleeker FE, Lamba S, Leenstra S et al (2009) IDH1 mutations at residue p.R132 (IDH1(R132)) occur frequently in high-grade gliomas but not in other solid tumors. Hum Mutat 30:7–11CrossRefPubMed Bleeker FE, Lamba S, Leenstra S et al (2009) IDH1 mutations at residue p.R132 (IDH1(R132)) occur frequently in high-grade gliomas but not in other solid tumors. Hum Mutat 30:7–11CrossRefPubMed
3.
go back to reference Blumcke I, Muller S, Buslei R et al (2004) Microtubule-associated protein-2 immunoreactivity: a useful tool in the differential diagnosis of low-grade neuroepithelial tumors. Acta Neuropathol 108:89–96CrossRefPubMed Blumcke I, Muller S, Buslei R et al (2004) Microtubule-associated protein-2 immunoreactivity: a useful tool in the differential diagnosis of low-grade neuroepithelial tumors. Acta Neuropathol 108:89–96CrossRefPubMed
4.
go back to reference Capper D, Weissert S, Balss J et al (2010) Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors. Brain Pathol 20:245–254CrossRefPubMed Capper D, Weissert S, Balss J et al (2010) Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors. Brain Pathol 20:245–254CrossRefPubMed
5.
go back to reference Capper D, Zentgraf H, Balss J et al (2009) Monoclonal antibody specific for IDH1 R132H mutation. Acta Neuropathol 118:599–601CrossRefPubMed Capper D, Zentgraf H, Balss J et al (2009) Monoclonal antibody specific for IDH1 R132H mutation. Acta Neuropathol 118:599–601CrossRefPubMed
6.
go back to reference Chou S, Varikatt W, Dexter M et al (2010) Extraventricular neurocytoma with atypical features and ganglionic differentiation. J Clin Neurosci 17:920–922CrossRefPubMed Chou S, Varikatt W, Dexter M et al (2010) Extraventricular neurocytoma with atypical features and ganglionic differentiation. J Clin Neurosci 17:920–922CrossRefPubMed
7.
go back to reference Dang L, White DW, Gross S et al (2009) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462:739–744CrossRefPubMed Dang L, White DW, Gross S et al (2009) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462:739–744CrossRefPubMed
8.
go back to reference Fujisawa H, Marukawa K, Hasegawa M et al (2002) Genetic differences between neurocytoma and dysembryoplastic neuroepithelial tumor and oligodendroglial tumors. J Neurosurg 97:1350–1355CrossRefPubMed Fujisawa H, Marukawa K, Hasegawa M et al (2002) Genetic differences between neurocytoma and dysembryoplastic neuroepithelial tumor and oligodendroglial tumors. J Neurosurg 97:1350–1355CrossRefPubMed
9.
go back to reference Hartmann C, Meyer J, Balss J et al (2009) Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas. Acta Neuropathol 118:469–474CrossRefPubMed Hartmann C, Meyer J, Balss J et al (2009) Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas. Acta Neuropathol 118:469–474CrossRefPubMed
10.
go back to reference Ichimura K, Pearson DM, Kocialkowski S et al (2009) IDH1 mutations are present in the majority of common adult gliomas but are rare in primary glioblastomas. Neuro Oncol 11:341–347CrossRefPubMed Ichimura K, Pearson DM, Kocialkowski S et al (2009) IDH1 mutations are present in the majority of common adult gliomas but are rare in primary glioblastomas. Neuro Oncol 11:341–347CrossRefPubMed
11.
go back to reference Idbaih A, Marie Y, Pierron G et al (2005) Two types of chromosome 1p losses with opposite significance in gliomas. Ann Neurol 58:483–487CrossRefPubMed Idbaih A, Marie Y, Pierron G et al (2005) Two types of chromosome 1p losses with opposite significance in gliomas. Ann Neurol 58:483–487CrossRefPubMed
12.
go back to reference Koperek O, Gelpi E, Birner P et al (2004) Value and limits of immunohistochemistry in differential diagnosis of clear cell primary brain tumors. Acta Neuropathol 108:24–30CrossRefPubMed Koperek O, Gelpi E, Birner P et al (2004) Value and limits of immunohistochemistry in differential diagnosis of clear cell primary brain tumors. Acta Neuropathol 108:24–30CrossRefPubMed
13.
go back to reference Korshunov A, Meyer J, Capper D et al (2009) Combined molecular analysis of BRAF and IDH1 distinguishes pilocytic astrocytoma from diffuse astrocytoma. Acta Neuropathol 118:401–405CrossRefPubMed Korshunov A, Meyer J, Capper D et al (2009) Combined molecular analysis of BRAF and IDH1 distinguishes pilocytic astrocytoma from diffuse astrocytoma. Acta Neuropathol 118:401–405CrossRefPubMed
14.
go back to reference Kreiger PA, Okada Y, Simon S et al (2005) Losses of chromosomes 1p and 19q are rare in pediatric oligodendrogliomas. Acta Neuropathol 109:387–392CrossRefPubMed Kreiger PA, Okada Y, Simon S et al (2005) Losses of chromosomes 1p and 19q are rare in pediatric oligodendrogliomas. Acta Neuropathol 109:387–392CrossRefPubMed
15.
go back to reference Kuhlmann T, Gutenberg A, Schulten HJ et al (2008) Nogo-a expression in glial CNS tumors: a tool to differentiate between oligodendrogliomas and other gliomas? Am J Surg Pathol 32:1444–1453CrossRefPubMed Kuhlmann T, Gutenberg A, Schulten HJ et al (2008) Nogo-a expression in glial CNS tumors: a tool to differentiate between oligodendrogliomas and other gliomas? Am J Surg Pathol 32:1444–1453CrossRefPubMed
16.
go back to reference Labussiere M, Idbaih A, Wang XW et al (2010) All the 1p19q codeleted gliomas are mutated on IDH1 or IDH2. Neurology 74:1886–1890CrossRefPubMed Labussiere M, Idbaih A, Wang XW et al (2010) All the 1p19q codeleted gliomas are mutated on IDH1 or IDH2. Neurology 74:1886–1890CrossRefPubMed
17.
go back to reference Louis DN, Ohgaki H, Wiestler OD et al (2007) WHO classification of tumors of the central nervous system. IARC, Lyon Louis DN, Ohgaki H, Wiestler OD et al (2007) WHO classification of tumors of the central nervous system. IARC, Lyon
18.
go back to reference Mardis ER, Ding L, Dooling DJ et al (2009) Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med 361:1058–1066CrossRefPubMed Mardis ER, Ding L, Dooling DJ et al (2009) Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med 361:1058–1066CrossRefPubMed
19.
go back to reference Mrak RE, Yasargil MG, Mohapatra G et al (2004) Atypical extraventricular neurocytoma with oligodendroglioma-like spread and an unusual pattern of chromosome 1p and 19q loss. Hum Pathol 35:1156–1159CrossRefPubMed Mrak RE, Yasargil MG, Mohapatra G et al (2004) Atypical extraventricular neurocytoma with oligodendroglioma-like spread and an unusual pattern of chromosome 1p and 19q loss. Hum Pathol 35:1156–1159CrossRefPubMed
20.
go back to reference Mueller W, Lass U, Veelken J et al (2006) 45-year-old male with symptomatic mass in the frontal lobe. Brain Pathol 16:89–90, 93 Mueller W, Lass U, Veelken J et al (2006) 45-year-old male with symptomatic mass in the frontal lobe. Brain Pathol 16:89–90, 93
21.
go back to reference Mut M, Guler-Tezel G, Lopes MB et al (2005) Challenging diagnosis: oligodendroglioma versus extraventricular neurocytoma. Clin Neuropathol 24:225–229PubMed Mut M, Guler-Tezel G, Lopes MB et al (2005) Challenging diagnosis: oligodendroglioma versus extraventricular neurocytoma. Clin Neuropathol 24:225–229PubMed
22.
go back to reference Ng H, Ko H, Tse C (1994) Immunohistochemical and ultrastructural studies of oligodendrogliomas revealed features of neuronal differentiation. Int J Surg Pathol 2:47–56CrossRef Ng H, Ko H, Tse C (1994) Immunohistochemical and ultrastructural studies of oligodendrogliomas revealed features of neuronal differentiation. Int J Surg Pathol 2:47–56CrossRef
23.
go back to reference Nobusawa S, Watanabe T, Kleihues P et al (2009) IDH1 mutations as molecular signature and predictive factor of secondary glioblastomas. Clin Cancer Res 15:6002–6007CrossRefPubMed Nobusawa S, Watanabe T, Kleihues P et al (2009) IDH1 mutations as molecular signature and predictive factor of secondary glioblastomas. Clin Cancer Res 15:6002–6007CrossRefPubMed
24.
go back to reference Ohgaki H, Kleihues P (2005) Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol 64:479–489PubMed Ohgaki H, Kleihues P (2005) Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol 64:479–489PubMed
25.
go back to reference Perry A, Burton SS, Fuller GN et al (2010) Oligodendroglial neoplasms with ganglioglioma-like maturation: a diagnostic pitfall. Acta Neuropathol 120:237–252CrossRefPubMed Perry A, Burton SS, Fuller GN et al (2010) Oligodendroglial neoplasms with ganglioglioma-like maturation: a diagnostic pitfall. Acta Neuropathol 120:237–252CrossRefPubMed
26.
go back to reference Perry A, Fuller CE, Banerjee R et al (2003) Ancillary FISH analysis for 1p and 19q status: preliminary observations in 287 gliomas and oligodendroglioma mimics. Front Biosci 8:a1–a9CrossRefPubMed Perry A, Fuller CE, Banerjee R et al (2003) Ancillary FISH analysis for 1p and 19q status: preliminary observations in 287 gliomas and oligodendroglioma mimics. Front Biosci 8:a1–a9CrossRefPubMed
27.
go back to reference Perry A, Scheithauer BW, Macaulay RJ et al (2002) Oligodendrogliomas with neurocytic differentiation. A report of 4 cases with diagnostic and histogenetic implications. J Neuropathol Exp Neurol 61:947–955PubMed Perry A, Scheithauer BW, Macaulay RJ et al (2002) Oligodendrogliomas with neurocytic differentiation. A report of 4 cases with diagnostic and histogenetic implications. J Neuropathol Exp Neurol 61:947–955PubMed
28.
go back to reference Preusser M, Budka H, Rossler K et al (2007) OLIG2 is a useful immunohistochemical marker in differential diagnosis of clear cell primary CNS neoplasms. Histopathology 50:365–370CrossRefPubMed Preusser M, Budka H, Rossler K et al (2007) OLIG2 is a useful immunohistochemical marker in differential diagnosis of clear cell primary CNS neoplasms. Histopathology 50:365–370CrossRefPubMed
29.
go back to reference Preusser M, Laggner U, Haberler C et al (2006) Comparative analysis of NeuN immunoreactivity in primary brain tumours: conclusions for rational use in diagnostic histopathology. Histopathology 48:438–444CrossRefPubMed Preusser M, Laggner U, Haberler C et al (2006) Comparative analysis of NeuN immunoreactivity in primary brain tumours: conclusions for rational use in diagnostic histopathology. Histopathology 48:438–444CrossRefPubMed
30.
go back to reference Pusch S, Sahm F, Meyer J et al (2010) Glioma IDH1 mutation patterns off the beaten track. Neuropathol Appl Neurobiol Pusch S, Sahm F, Meyer J et al (2010) Glioma IDH1 mutation patterns off the beaten track. Neuropathol Appl Neurobiol
31.
go back to reference Raghavan R, Balani J, Perry A et al (2003) Pediatric oligodendrogliomas: a study of molecular alterations on 1p and 19q using fluorescence in situ hybridization. J Neuropathol Exp Neurol 62:530–537PubMed Raghavan R, Balani J, Perry A et al (2003) Pediatric oligodendrogliomas: a study of molecular alterations on 1p and 19q using fluorescence in situ hybridization. J Neuropathol Exp Neurol 62:530–537PubMed
32.
go back to reference Remmele W, Stegner HE (1987) Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue. Pathologe 8:138–140PubMed Remmele W, Stegner HE (1987) Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue. Pathologe 8:138–140PubMed
33.
go back to reference Rodriguez FJ, Mota RA, Scheithauer BW et al (2009) Interphase cytogenetics for 1p19q and t(1;19)(q10;p10) may distinguish prognostically relevant subgroups in extraventricular neurocytoma. Brain Pathol 19:623–629CrossRefPubMed Rodriguez FJ, Mota RA, Scheithauer BW et al (2009) Interphase cytogenetics for 1p19q and t(1;19)(q10;p10) may distinguish prognostically relevant subgroups in extraventricular neurocytoma. Brain Pathol 19:623–629CrossRefPubMed
34.
go back to reference Rodriguez FJ, Scheithauer BW, Robbins PD et al (2007) Ependymomas with neuronal differentiation: a morphologic and immunohistochemical spectrum. Acta Neuropathol 113:313–324CrossRefPubMed Rodriguez FJ, Scheithauer BW, Robbins PD et al (2007) Ependymomas with neuronal differentiation: a morphologic and immunohistochemical spectrum. Acta Neuropathol 113:313–324CrossRefPubMed
35.
go back to reference Sahm F, Capper D, Meyer J et al (2010) Immunohistochemical analysis of 1844 human epithelial and hematopoietic tumors and sarcomas for IDH1R132H mutation. Histopathology Sahm F, Capper D, Meyer J et al (2010) Immunohistochemical analysis of 1844 human epithelial and hematopoietic tumors and sarcomas for IDH1R132H mutation. Histopathology
36.
go back to reference Sanson M, Marie Y, Paris S et al (2009) Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol 27:4150–4154CrossRefPubMed Sanson M, Marie Y, Paris S et al (2009) Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol 27:4150–4154CrossRefPubMed
37.
go back to reference Soylemezoglu F, Onder S, Tezel GG et al (2003) Neuronal nuclear antigen (NeuN): a new tool in the diagnosis of central neurocytoma. Pathol Res Pract 199:463–468CrossRefPubMed Soylemezoglu F, Onder S, Tezel GG et al (2003) Neuronal nuclear antigen (NeuN): a new tool in the diagnosis of central neurocytoma. Pathol Res Pract 199:463–468CrossRefPubMed
38.
go back to reference Takeuchi H, Kubota T, Kitai R et al (2009) Chromosome 1p and 19q deletions in malignant glioneuronal tumors with oligodendroglioma-like component. J Neurooncol 91:33–38CrossRefPubMed Takeuchi H, Kubota T, Kitai R et al (2009) Chromosome 1p and 19q deletions in malignant glioneuronal tumors with oligodendroglioma-like component. J Neurooncol 91:33–38CrossRefPubMed
39.
go back to reference Vajtai I, Arnold M, Vassella E (2005) Oligodendroglioma with neurocytic differentiation and characteristic loss of heterozygosity on chromosomes 1p and 19q. Acta Neuropathol 110:520–522CrossRefPubMed Vajtai I, Arnold M, Vassella E (2005) Oligodendroglioma with neurocytic differentiation and characteristic loss of heterozygosity on chromosomes 1p and 19q. Acta Neuropathol 110:520–522CrossRefPubMed
40.
go back to reference Vallat-Decouvelaere AV, Gauchez P, Varlet P et al (2000) So-called malignant and extra-ventricular neurocytomas: reality or wrong diagnosis? A critical review about two overdiagnosed cases. J Neurooncol 48:161–172CrossRefPubMed Vallat-Decouvelaere AV, Gauchez P, Varlet P et al (2000) So-called malignant and extra-ventricular neurocytomas: reality or wrong diagnosis? A critical review about two overdiagnosed cases. J Neurooncol 48:161–172CrossRefPubMed
41.
go back to reference Ward PS, Patel J, Wise DR et al (2010) The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer Cell 17:225–234CrossRefPubMed Ward PS, Patel J, Wise DR et al (2010) The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer Cell 17:225–234CrossRefPubMed
42.
go back to reference Watanabe T, Nobusawa S, Kleihues P et al (2009) IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am J Pathol 174:1149–1153CrossRefPubMed Watanabe T, Nobusawa S, Kleihues P et al (2009) IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am J Pathol 174:1149–1153CrossRefPubMed
43.
go back to reference Wharton SB, Chan KK, Hamilton FA et al (1998) Expression of neuronal markers in oligodendrogliomas: an immunohistochemical study. Neuropathol Appl Neurobiol 24:302–308CrossRefPubMed Wharton SB, Chan KK, Hamilton FA et al (1998) Expression of neuronal markers in oligodendrogliomas: an immunohistochemical study. Neuropathol Appl Neurobiol 24:302–308CrossRefPubMed
44.
go back to reference Wolf HK, Buslei R, Blumcke I et al (1997) Neural antigens in oligodendrogliomas and dysembryoplastic neuroepithelial tumors. Acta Neuropathol 94:436–443CrossRefPubMed Wolf HK, Buslei R, Blumcke I et al (1997) Neural antigens in oligodendrogliomas and dysembryoplastic neuroepithelial tumors. Acta Neuropathol 94:436–443CrossRefPubMed
45.
go back to reference Yan H, Parsons DW, Jin G et al (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765–773CrossRefPubMed Yan H, Parsons DW, Jin G et al (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765–773CrossRefPubMed
Metadata
Title
Mutation-specific IDH1 antibody differentiates oligodendrogliomas and oligoastrocytomas from other brain tumors with oligodendroglioma-like morphology
Authors
David Capper
David Reuss
Jens Schittenhelm
Christian Hartmann
Juliane Bremer
Felix Sahm
Patrick N. Harter
Astrid Jeibmann
Andreas von Deimling
Publication date
01-02-2011
Publisher
Springer-Verlag
Published in
Acta Neuropathologica / Issue 2/2011
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-010-0770-2

Other articles of this Issue 2/2011

Acta Neuropathologica 2/2011 Go to the issue