title: IDH mutation status impact on in vivo hypoxia biomarkers expression: new insights from a clinical, nuclear imaging and immunohistochemical study in 33 glioma patients.
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 (18)F-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.
authors.affiliation: Hôpital de la Timone, Service de Neurochirurgie, Assistance Publique-Hôpitaux de Marseille, 13000 Marseille, France. philippe.metellus@mail.ap-hm.fr
authors.forename: Philippe
authors.initials: P
authors.lastname: Metellus
authors.forename: Carole
authors.initials: C
authors.lastname: Colin
authors.forename: David
authors.initials: D
authors.lastname: Taieb
authors.forename: Eric
authors.initials: E
authors.lastname: Guedj
authors.forename: Isabelle
authors.initials: I
authors.lastname: Nanni-Metellus
authors.forename: Andre Maues
authors.initials: AM
authors.lastname: de Paula
authors.forename: Cécile
authors.initials: C
authors.lastname: Colavolpe
authors.forename: Stephane
authors.initials: S
authors.lastname: Fuentes
authors.forename: Henry
authors.initials: H
authors.lastname: Dufour
authors.forename: Marylin
authors.initials: M
authors.lastname: Barrie
authors.forename: Olivier
authors.initials: O
authors.lastname: Chinot
authors.forename: L'houcine
authors.initials: L
authors.lastname: Ouafik
authors.forename: Dominique
authors.initials: D
authors.lastname: Figarella-Branger
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human