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

  • CLINICAL STUDY – PATIENT STUDY
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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.

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Acknowledgments

We are grateful to F. Frassineti and D. Intagliata for excellent technical assistance, and to C. Bequet-Boucard and C. Courdy for providing clinical information regarding the patients. This work was supported was supported by grants from INSERM (CRO2–UMR911), the INCA (Procan), the Association pour la Recherche sur les Tumeurs Cérébrales (ARTC-Sud), and the Groupement des Entreprises Françaises dans la Lutte contre le Cancer (GEFLUC).

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Authors and Affiliations

  1. Hôpital de la Timone, Service de Neurochirurgie, Assistance Publique-Hôpitaux de Marseille, 13000, Marseille, France

    Philippe Metellus, Stephane Fuentes & Henry Dufour

  2. INSERM, UMR 911, 13000, Marseille, France

    Philippe Metellus, Carole Colin, Olivier Chinot, L’Houcine Ouafik & Dominique Figarella-Branger

  3. Faculté de Médecine, Aix-Marseille Université, 13000, Marseille, France

    Philippe Metellus, Carole Colin, Olivier Chinot, L’Houcine Ouafik & Dominique Figarella-Branger

  4. Hôpital de la Timone, Service Central de Biophysique et Médecine nucléaire, Assistance Publique-Hôpitaux de Marseille, 13000, Marseille, France

    David Taieb & Eric Guedj

  5. Laboratoire de Transfert D’oncologie Biologique, AP-HM, Marseille, France

    Isabelle Nanni-Metellus & L’Houcine Ouafik

  6. Hôpital de la Timone, Service d’Anatomie Pathologique et de Neuropathologie, Assistance Publique-Hôpitaux de Marseille, 13000, Marseille, France

    Andre Maues de Paula, Cécile Colavolpe & Dominique Figarella-Branger

  7. Hôpital de la Timone, Unité de Neurooncologie, Assistance Publique-Hôpitaux de Marseille, 13000, Marseille, France

    Marylin Barrie & Olivier Chinot

  8. Service de Neurochirurgie, Hôpital de la TIMONE, 264, rue Saint-Pierre, 13385, Cedex Marseille, France

    Philippe Metellus

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  1. Philippe Metellus
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Correspondence to Philippe Metellus.

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Philippe Metellus and Carole Colin contributed equally to this study.

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Metellus, P., Colin, C., Taieb, D. et al. IDH mutation status impact on in vivo hypoxia biomarkers expression: new insights from a clinical, nuclear imaging and immunohistochemical study in 33 glioma patients. J Neurooncol 105, 591–600 (2011). https://doi.org/10.1007/s11060-011-0625-2

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  • DOI: https://doi.org/10.1007/s11060-011-0625-2

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