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Hypoxia-inducible factor-1-regulated protein expression and oligodendroglioma patient outcome: comparison with established biomarkers and preoperative UCSF low-grade scoring system

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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.

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Acknowledgments

We thank Kristin Kraus, Sheryl Tripp, and Xiang (Lara) Li for assistance with editing, immunohistochemistry methods, and organizing some of the tables and K–M plots, respectively. Funding was provided in part by Huntsman Cancer Institute, Cancer Control and Population Sciences Pilot Grant CCPS HCI-Hu PI 22255.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Division of Pediatric Oncology, Department of Pediatrics, University of Utah, Salt Lake City, UT, USA

    Shirley Abraham

  2. Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA

    Nan Hu

  3. Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA

    Nan Hu & Randy Jensen

  4. Departments of Neurosurgery, Radiation Oncology, and Oncological Sciences, Clinical Neuroscience Center, University of Utah, Fifth Floor, 175 North Medical Drive, Salt Lake City, UT, 84132, USA

    Randy Jensen

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  1. Shirley Abraham
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Correspondence to Randy Jensen.

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Abraham, S., Hu, N. & Jensen, R. Hypoxia-inducible factor-1-regulated protein expression and oligodendroglioma patient outcome: comparison with established biomarkers and preoperative UCSF low-grade scoring system. J Neurooncol 108, 459–468 (2012). https://doi.org/10.1007/s11060-012-0839-y

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