Hypoxia-regulated Protein Expression, Patient Characteristics, and Preoperative Imaging As Predictors of Survival in Adults with Glioblastoma Multiforme

Background: Regions of hypoxia within glioblastoma multiforme (GBM) are common and may influence a tumor's aggressiveness, response to treatment, and the patient's overall survival. In this study, the authors examined 4 markers of hypoxia (hypoxia-inducible factor 1 [HIF-1alpha], glucose transporter 1 [GLUT-1], vascular endothelial growth factor [VEGF], and carbonic anhydrase 9 [CA IX]), cellular proliferation and microvascular density (MVD) indices, extent of surgical resection, and preoperative imaging characteristics and compared them with the overall survival rates of adults with GBM.

Methods: In this retrospective cohort study, patients who had lower grade astrocytomas were compared with patients who had GBM to verify that the methods used could establish differences between tumor grades. By using preoperative imaging, the amount of necrosis was established versus the overall tumor area. The authors also compared preoperative images with postoperative images to define the amount of tumor resected; and they compared molecular markers, proliferation, MVD, and imaging studies with survival among patients who had GBM.

Results: The hypoxia-regulated molecules (HRMs) and indices for MVD and cellular proliferation were associated significantly with tumor grade. Survival was improved when >or=95% of the tumor was resected. Although the total tumor area was associated with overall survival, no differences were observed when the amount of necrosis or a tumor necrosis index (area of necrosis/area of tumor) was compared with survival. The findings indicated that GLUT-1 and VEGF were correlated with survival after controlling for age.

Conclusions: Tumor grade was differentiated with HRMs, MVD, and proliferation, but only GLUT-1 predicted survival in this group of patients with GBM. The results suggested that GLUT-1 may be an important independent prognostic indicator.