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

• Published in: Journal of neuro-oncology Vol. 105; no. 3; pp. 591 - 600
• Main Authors: Metellus, Philippe, Colin, Carole, Taieb, David, Guedj, Eric, Nanni-Metellus, Isabelle, de Paula, Andre Maues, Colavolpe, Cécile, Fuentes, Stephane, Dufour, Henry, Barrie, Marylin, Chinot, Olivier, Ouafik, L’Houcine, Figarella-Branger, Dominique
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-12-2011; Springer Nature B.V; Springer Verlag
• Subjects: Adult; Aged; biomarkers; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Brain Neoplasms - diagnostic imaging; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain tumors; Cancer; Carbonate dehydratase; Caspase-3; Central nervous system; Clinical Study–Patient Study; Codons; Data processing; DNA Mutational Analysis; Enzymes; Female; Gene deletion; Glioma; Glioma - diagnostic imaging; Glioma - genetics; Glioma - metabolism; Glucose transporter; Humans; Hypoxia; Hypoxia - genetics; Hypoxia - metabolism; Hypoxia-inducible factor 1 alpha; Immunohistochemistry; Isocitrate dehydrogenase; Isocitrate Dehydrogenase - genetics; Life Sciences; Male; Medicine; Medicine & Public Health; Middle Aged; Mutation; Neoplasm Staging; Neurology; Oncology; p53 protein; Positron emission tomography; Retrospective Studies; Tumors; Young Adult; Glucose transporter 1; Isocitrate dehydrogenase-1(IDH1); Carbonic anhydrase IX; Hypoxia-inducible factor 1; Active caspase 3
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1007/s11060-011-0625-2

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.