Mutations in IDH1/2 Genes Predict Better Disease Outcome of Glioma Patients-A Study from Western India

Abstract

Introduction: Isocitrate Dehydrogenase (IDH) plays an important role in cellular metabolism. In gliomas, the mutational status of IDH1/2 genes have paramount significance, however, study from Western India is limited. Therefore, the current study we sought to explore the clinical impact of IDH1/2 mutations for glioma patients from Western India. Materials and Method: A total of 50 pre-therapeutic, histopathologically confirmed patients with astrocytoma tumors were included and IDH1/2 mutations were detected using real-time PCR. IDH1/2 mutations were correlated with clinicopathological parameters and disease outcome. Data was evaluated by SPSS software. Results: The overall incidence of IDH1/2 mutations was noted in 24% (12/50) of glioma patients. Out of 12 patients whose tumors showed IDH mutations, 83% patients have IDH1 mutations, whereas 17% showed IDH2 mutation. Further, in IDH1 mutations, IDH1 R132H & IDH1 R132C mutations were noted in, 80% and 20% of patients, respectively. When correlated with clinicopathological parameters, significant inverse correlation was found with patients age (χ2= 9.75, r = -0.476, p=0.001) and grade of tumors (χ2=17.51, r =-0.636, p=0.0001). In Kaplan-Meier survival analysis, a part from age (Log rank=5.443, p=0.020), IDH mutation status (Log rank=3.855, p=0.050), and both, IDH mutation and low grade glioma tumors (Log rank=6.492, p=0.039) remained significant parameters for predicting better 24 months PFS and OS of glioma patients. However, in multivariate survival analysis using Cox Proportional Hazard Forward Stepwise Model, only combination of low grade glioma with presence of IDH mutation emerged at step one as positive significant independent prognostic factor that predict better PFS (HR=2.92, 95% CI=1.12-7.61, p=0.028) and OS (HR=3.0, 95% CI=1.45-6.19, p=0.003). Conclusion: Based on this data, we concluded that for glioma patients, apart from patients age, low grade tumors with presence of IDH mutations remained significant independent positive prognosticators and would be helpful to clinicians for better management of glioma patients.