Idh-1 Status and Venous Thromboembolism in Glioma Patients

Abstract

Background: Venous thromboembolic events (VTE) are common causes of morbidity and mortality in glioblastoma patients. Mutation in the isocitrate dehydrogenase 1 enzyme (IDH1) is frequent in secondary glioblastoma and results in altered metabolomics. Objectives: This study evaluates whether IDH-1 status correlates with incidence of VTE in glioblastoma patients. Methods: Observational study of 398 cases of patients with glioblastoma, who all underwent surgery in a regional Neurosurgical centre between April 2012 and December 2014. IDH -1 status and Tissue factor (F3) protein expression were assessed by immunohistochemistry. Deep venous thrombosis (DVT) and pulmonary embolism (PE) were diagnosed by Doppler ultrasound and pulmonary CT angiogram respectively. Results: 336 cases were wild type (WT) IDH-1 (94.1%) and 21 cases were IDH-1 mutated (R132H) (5.9%). 51 patients had a thromboembolic event (15.3%), with all cases of VTE in WT IDH-1 tumours, a rate of 21.8% within this group. IDH-1 status had a significant correlation with VTE (p=0.033 Fisher exact test). As expected, mutant IDH was associated with prolonged patient survival (p=0.024 Log rank). The mean expression in IDH-1 wild type GBM was 7.14 and in R132h mutant GBM was 4.87 (log2 scale). This was highly statistically significant with a corrected P value of less than 0.0001. Conclusion: A significant association exists between IDH1 status in glioblastoma patients and the risk of VTE. Patients with wild type IDH-1 appear at high risk of VTE and appropriate precautions should be considered