Clinicopathological Analysis of HIF-1alpha and TERT on Survival Outcome in Glioblastoma Patients: A prospective, single institution study

Abstract

Glioblastoma multiforme is a highly malignant and aggressive primary brain tumor with a dismal prognosis. We studied the association of immunohistochemical expression of hypoxia inducible factor-1 alpha (HIF-1α), telomerase reverse transcriptase (TERT), isocitrate dehydrogenase 1 (IDH1) and tumor protein p53 with overall survival (OS) in glioblastoma patients uniformly treated by standard of care, with adequate follow-up. In 87 patient samples studied, 59 were male and 28 were female. The median age was 55 years. The median follow-up was 27.7 months and the median overall survival was 14.9 months. Nuclear staining of HIF-1α was expressed in all samples and scored as strong in 42 (48%) and weak in 45 (52%). Multivariable Cox regression revealed strong HIF-1α expression as an independent poor prognostic factor (Hazard Ratio 2.12, 95% CI 1.20 - 3.74, P = 0.01). There was a statistically significant difference in OS (9.8 months vs. 16.3 months) between the “HIF-1α - strong and TERT - strong” and the “HIF-1α - weak and TERT - weak” patient subgroups, as evaluated by Kaplan-Meier analysis (P = 0.005). In our study, HIF-1α expression was an independent predictor of OS. The subgroup of patients with strong expression of both HIF-1α and TERT had the poorest prognosis.