Correlation of immunohistochemical expression of HIF-1alpha and IDH1 with clinicopathological and therapeutic data of moroccan glioblastoma and survival analysis

Abstract

Introduction Glioblastomas are aggressive primary intracranial tumours of the central nervous system causing significant mortality and morbidity worldwide. Objective This study aims to evaluate the prognostic value of tissue expression by immunostaining of hypoxia-inducible factor (HIF-1α), isocitrate dehydrogenase 1 (IDH1), and tumour protein p53 in glioblastoma in Moroccan patients. The association of HIF-1α, IDH1, and p53 expression with the clinicopathological data and overall patient survival (OS) was also evaluated. Materials and methods Confirmed glioblastomas were included in this study. Twenty-two tissue samples were obtained by neurosurgical intervention resulting from total resection, and subtotal resection or biopsy. Karnofsky index, histological type of tumour, and the status of IDH1, p53 protein, and HIF-1α expression by immunostaining were reported. Results The majority of the patients were males (64%) with a sex ratio of 1.75. The average age was 54 ± 13. Median follow-up was 10.10 months and median overall survival was 10 months. The expression of HIF-1α was high in 10 samples (45%) and low in 12 (55%). There was a statistically significant difference in OS of 85% at 12 months for the subgroup of patients “HIF-1α negative IDH1 positive” p = 0.038, the unadjusted analysis showed that the group “HIF-1α positive, IDH1 positive” was a poor prognostic factor, the HR was 0.08 (95% CI: 0.009–0.756, p = 0.027). Conclusion Patients with negative HIF-1α expression and positive IDH1 expression have a better prognosis, suggesting that these two biomarkers may be useful in the search for new approaches for targeted therapy in glioblastoma.

Prognostic significance of HIF1-α immunohistochemical expression in gliomas and it's relation to IDH1 mutation status

“…Liu et al [28] study also found a significant difference of the HIF-1α expression and IDH1 mutation (p-value = 0.012). In grade 4 gliomas studied by Sfifou et al [23] most cases expressed HIF-1α (70%) were IDH1 R132H -ve.…”

“…The expression of HIF-1α indicates tumor hypoxia, which plays an essential role in initiation, progression and also therapy resistance. High HIF-1α is associated with bad prognosis in many tumors [23].…”

Molecular and Circulating Biomarkers in Patients with Glioblastoma

“…The group with "negative HIF-1α and positive IDH1" illustrated a better outcome with 85% survival rate at 12 months. Nevertheless, the patients with "positive HIF-1α and negative IDH1" expressed the worst prognosis with 18% survival [162].…”

“…In addition, hypoxia is a predominant feature involved in the development of the GBM microenvironment, considering its implication in the stability of HIF-1α. The latter is the hypoxia-inducible factor that has been identified as a major operator of the Warburg effect and the trigger in the occurrence of some solid tumors, including glioblastoma [162].…”

Therapeutic strategies of glioblastoma (GBM): The current advances in the molecular targets and bioactive small molecule compounds

“…In GBM patients, more than half were p35 positive, and DNA sequencing analysis showed that p53-positive microvascular proliferating cells were identical to TP53 mutations observed in primary tumors. The p53 protein is encoded by the TP53 gene, which is thought to be the most mutated gene in human tumors 116 . The components of the deregulated p53 pathway are related to the invasion, migration, proliferation, avoidance of apoptosis and stem cell properties of GBM cells.…”