Abstract
Gliomatosis cerebri (GC) constitutes a heterogenous group of conditions involving diffuse neoplastic glial cell infiltration of the brain. Management is difficult and an obvious challenge is to identify prognostic factors. Alpha-internexin (INA) expression, which is closely related to the 1p19q codeletion, is a strong prognostic marker in oligodendroglial tumors. Similarly, the R132H isocitrate dehydrogenase 1 IDH1 mutation, which can now be detected by use of a specific antibody, predicts better outcome in gliomas. In a retrospective series of 40 GC treated with up-front chemotherapy, we analyzed IDH1R132H mutant protein and INA immunohistochemical expression and correlated it with outcome; 17/40 GC expressed IDH1R132H and 10/40 GC expressed INA. IDH1R132H staining was strongly related to progression-free survival (42.3 vs. 15.5 months for positive IDH1R132H vs. negative tumors; P < 0.0001) and overall survival (73.9 vs. 23.6 months; P < 0.0001). This effect was independent of grade, histologic subtype, and INA expression (P < 0.001). Combined expression of IDH1R132H and INA was strongly associated with response to chemotherapy (100% vs. 36%; P = 0.003). These data strongly suggest that INA and IDH1R132H mutant protein immunohistochemical analysis is of a great prognostic value in biopsied GC.
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References
Levin N, Gomori JM, Siegal T (2004) Chemotherapy as initial treatment in gliomatosis cerebri: results with temozolomide. Neurology 63:354–356
Sanson M, Cartalat-Carel S, Taillibert S et al (2004) Initial chemotherapy in gliomatosis cerebri. Neurology 63:270–275
Kaloshi G, Everhard S, Laigle-Donadey F et al (2008) Genetic markers predictive of chemosensitivity and outcome in gliomatosis cerebri. Neurology 70:590–595
Kaloshi G, Guillevin R, Martin-Duverneuil N et al (2009) Gray matter involvement predicts chemosensitivity and prognosis in gliomatosis cerebri. Neurology 73:445–449
Ducray F, Criniere E, Idbaih A et al (2009) Alpha-internexin expression identifies 1p19q codeleted gliomas. Neurology 72:156–161
Yan H, Parsons DW, Jin G et al (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765–773
van den Bent MJ, Dubbink HJ, Marie Y et al (2010) IDH1 and IDH2 mutations are prognostic but not predictive for outcome in anaplastic oligodendroglial tumors: a report of the European Organization for Research and Treatment of Cancer Brain Tumor Group. Clin Cancer Res 16:1597–1604
Metellus P, Coulibaly B, Colin C et al (2010) Absence of IDH mutation identifies a novel radiologic and molecular subtype of WHO grade II gliomas with dismal prognosis. Acta Neuropathol 120:719–729
Houillier C, Wang X, Kaloshi G et al (2010) IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas. Neurology 75:1560–1566
Capper D, Zentgraf H, Balss J, Hartmann C, von Deimling A (2009) Monoclonal antibody specific for IDH1 R132H mutation. Acta Neuropathol 118:599–601
Capper D, Weissert S, Balss J et al (2010) Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors. Brain Pathol 20:245–254
Camelo-Piragua S, Jansen M, Ganguly A, Kim JC, Louis DN, Nutt CL (2010) Mutant IDH1-specific immunohistochemistry distinguishes diffuse astrocytoma from astrocytosis. Acta Neuropathol 119:509–511
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 27:4150–4154
Seiz M, Tuettenberg J, Meyer J et al (2010) Detection of IDH1 mutations in gliomatosis cerebri, but only in tumors with additional solid component: evidence for molecular subtypes. Acta Neuropathol 120:261–267
Horbinski C, Kofler J, Kelly LM, Murdoch GH, Nikiforova MN (2009) Diagnostic use of IDH1/2 mutation analysis in routine clinical testing of formalin-fixed, paraffin-embedded glioma tissues. J Neuropathol Exp Neurol 68:1319–1325
Ducray F, Idbaih A, de Reynies A et al (2008) Anaplastic oligodendrogliomas with 1p19q codeletion have a proneural gene expression profile. Mol Cancer 7:41
Labussière M, Wang XW, Marie Y et al (2010) IDH1/IDH2 is systematically mutated in 1p19q codeleted gliomas. Neurology 74:1886–1890
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Desestret, V., Ciccarino, P., Ducray, F. et al. Prognostic stratification of gliomatosis cerebri by IDH1R132H and INA expression. J Neurooncol 105, 219–224 (2011). https://doi.org/10.1007/s11060-011-0587-4
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DOI: https://doi.org/10.1007/s11060-011-0587-4