title: Hypoxia-inducible factor-1-regulated protein expression and oligodendroglioma patient outcome: comparison with established biomarkers and preoperative UCSF low-grade scoring system.
abstract: Methods for predicting outcome for patients with oligodendrogliomas and anaplastic oligodendrogliomas (AOs) are limited. Hypoxia-inducible factor-1α (HIF-1α) controls many proteins involved in glycolysis and angiogenesis including VEGF, Glut-1, and CA-IX. We examined whether expression of HIF-1α and other hypoxia-regulated molecules (HRM) can predict overall (OS) and progression-free (PFS) survival. We correlated these data with more established biomarkers and a published preoperative scoring system. We prospectively collected tissue samples and followed outcomes of 50 patients with oligodendrogliomas and 32 with AOs. Tumor tissues were stained for measures of proliferative index, microvascular density, IDH-1 mutational status, and HRMs. We retrospectively analyzed preoperative imaging and clinical data based on the UCSF Scoring System (good prognostic indicators: Karnofsky Performance Scale (KPS) score > 80, age < 50 years, tumor diameter < 4 cm, noneloquent tumor location) and correlated these with immunohistochemical markers, 1p19q chromosomal status, and compared both with patient PFS and OS. Mean follow-up was 85.6 ± 41.4 months. HRMs showed higher expression in AOs than in oligodendrogliomas. Both 1p19q codeletion and IDH-1 mutation predict outcome of patients with both oligodendroglioma and AO. The UCSF score is a strong predictor for oligodendrogliomas patient outcome and is strengthened by IDH-1 and 1p19q status. Glut-1 may be useful in predicting PFS in AOs. Proliferation index >5 for oligodendrogliomas and KPS ≤ 80 for AOs predict a worse prognosis. Immunohistochemical markers of HRMs show a significantly higher expression in anaplastic variants of oligodendrogliomas and may contribute to the prediction of survival in these patients.
authors.affiliation: Division of Pediatric Oncology, Department of Pediatrics, University of Utah, Salt Lake City, UT, USA.
authors.forename: Shirley
authors.initials: S
authors.lastname: Abraham
authors.forename: Nan
authors.initials: N
authors.lastname: Hu
authors.forename: Randy
authors.initials: R
authors.lastname: Jensen
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D060787:Neoplasm Grading; D009837:Oligodendroglioma / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality*; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human