CLINICAL STUDY – PATIENT STUDY

Journal of Neuro-Oncology

, Volume 105, Issue 3, pp 591-600

IDH mutation status impact on in vivo hypoxia biomarkers expression: new insights from a clinical, nuclear imaging and immunohistochemical study in 33 glioma patients

  • Philippe MetellusAffiliated withHôpital de la Timone, Service de Neurochirurgie, Assistance Publique-Hôpitaux de MarseilleINSERM, UMR 911Faculté de Médecine, Aix-Marseille UniversitéService de Neurochirurgie, Hôpital de la TIMONE Email author 
  • , Carole ColinAffiliated withINSERM, UMR 911Faculté de Médecine, Aix-Marseille Université
  • , David TaiebAffiliated withHôpital de la Timone, Service Central de Biophysique et Médecine nucléaire, Assistance Publique-Hôpitaux de Marseille
  • , Eric GuedjAffiliated withHôpital de la Timone, Service Central de Biophysique et Médecine nucléaire, Assistance Publique-Hôpitaux de Marseille
  • , Isabelle Nanni-MetellusAffiliated withLaboratoire de Transfert D’oncologie Biologique, AP-HM
  • , Andre Maues de PaulaAffiliated withHôpital de la Timone, Service d’Anatomie Pathologique et de Neuropathologie, Assistance Publique-Hôpitaux de Marseille
  • , Cécile ColavolpeAffiliated withHôpital de la Timone, Service d’Anatomie Pathologique et de Neuropathologie, Assistance Publique-Hôpitaux de Marseille
  • , Stephane FuentesAffiliated withHôpital de la Timone, Service de Neurochirurgie, Assistance Publique-Hôpitaux de Marseille
  • , Henry DufourAffiliated withHôpital de la Timone, Service de Neurochirurgie, Assistance Publique-Hôpitaux de Marseille
    • , Marylin BarrieAffiliated withHôpital de la Timone, Unité de Neurooncologie, Assistance Publique-Hôpitaux de Marseille
    • , Olivier ChinotAffiliated withINSERM, UMR 911Faculté de Médecine, Aix-Marseille UniversitéHôpital de la Timone, Unité de Neurooncologie, Assistance Publique-Hôpitaux de Marseille
    • , L’Houcine OuafikAffiliated withINSERM, UMR 911Faculté de Médecine, Aix-Marseille UniversitéLaboratoire de Transfert D’oncologie Biologique, AP-HM
    • , Dominique Figarella-BrangerAffiliated withINSERM, UMR 911Faculté de Médecine, Aix-Marseille UniversitéHôpital de la Timone, Service d’Anatomie Pathologique et de Neuropathologie, Assistance Publique-Hôpitaux de Marseille

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Abstract

Mutations in the gene encoding isocitrate dehydrogenase enzyme isoforms 1 (IDH1) and 2 (IDH2) have recently been identified in a large proportion of glial tumors of the CNS, but their mechanistic role in tumor development remains unclear. Here, we assessed the actual impact of IDH1 and IDH2 mutations in patients harboring WHO grade II and III gliomas. We sequenced IDH1 at codon 132 and IDH2 at codon 172 in 33 patients with WHO grade II and III gliomas who benefited from a preoperative 18F-FDG positron emission tomography (PET). Immunohistochemical expression of Hypoxia Inducible Factor-1alpha (HIF-1α), Carbonic Anhydrase IX (CAIX), Glucose Transporter 1 (GLUT1) and Caspase 3 active form (CASP3) along with the R132HIDH1 mutation was assessed in all cases as well as 1p/19q deletion status and p53 expression. HIF-1α expression was found in 15% of IDH-mutated compared to 7.7% of IDH-nonmutated tumors (P = 0.954). Also, GLUT-1 positive staining was found in 5% of IDH-mutated and in 7.1% of IDH-nonmutated tumors (P = 0.794). Finally, CA-IX expression was found in 15% of IDH-mutated and in 7.7% of IDH-nonmutated tumors (P = 0.484). The combined expression of these three hypoxic markers was found in two WHO grade III tumors, one of which was IDH-mutated whereas the other was IDH-nonmutated (P = 0.794). In IDH-mutated tumors, the median SUVmax ratio was 2.24 versus 2.15 in IDH-nonmutated tumors (P = 0.775). Together, these data question the actual relationship between IDH mutation status and in vivo hypoxic biomarkers expression in WHO grade II and III gliomas.

Keywords

Active caspase 3 Carbonic anhydrase IX Glucose transporter 1 Isocitrate dehydrogenase-1(IDH1) Hypoxia-inducible factor 1