J Cancer 2019; 10(11):2397-2406. doi:10.7150/jca.32909

Research Paper

Clinicopathological Analysis of HIF-1alpha and TERT on Survival Outcome in Glioblastoma Patients: A Prospective, Single Institution Study

Mahadev Potharaju1, Anugraha Mathavan1, Balamurugan Mangaleswaran2, Sushama Patil3, Reginald John2, Siddhartha Ghosh2, Chandrasekhar Kalavakonda2, Mitra Ghosh3, Rama Shanker Verma4✉

1. Department of Radiation Oncology, Apollo Speciality Hospitals, Chennai - 600035, India
2. Department of Neurosurgery, Apollo Speciality Hospitals, Chennai - 600035, India
3. Department of Pathology, Apollo Speciality Hospitals, Chennai - 600035, India
4. Indian Institute of Technology - Madras, Chennai - 600036, India

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Potharaju M, Mathavan A, Mangaleswaran B, Patil S, John R, Ghosh S, Kalavakonda C, Ghosh M, Verma RS. Clinicopathological Analysis of HIF-1alpha and TERT on Survival Outcome in Glioblastoma Patients: A Prospective, Single Institution Study. J Cancer 2019; 10(11):2397-2406. doi:10.7150/jca.32909. Available from http://www.jcancer.org/v10p2397.htm

File import instruction

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.

Keywords: glioblastoma, hypoxia, HIF-1α, TERT, IDH1, immunohistochemistry