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

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, in the current study, we sought to explore the clinical impact of IDH1/2 mutations on glioma patients from Western India.

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 outcomes. Data were evaluated by SPSS software.

 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% of 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, a 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, apart 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 the Cox Proportional Hazard Forward Stepwise Model, only a combination of low-grade glioma with the presence of IDH mutation emerged at step one as a 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).

Based on this data, we concluded that for glioma patients, apart from patients' age, low-grade tumors with the presence of IDH mutations remained significant independent positive prognosticators and would be helpful to clinicians for better management of glioma patients.