gms | German Medical Science

Objectives: Venous thromboembolic events (VTE) are common causes of morbidity and mortality in glioblastoma patients. Mutation in the isocitrate dehydrogenase-1 gene (IDH1) is frequent in secondary glioblastoma and results in altered metabolomics. This study evaluates whether IDH-1 status correlates with incidence of VTE in glioblastoma patients.

Methods: We retrospectively analyzed case notes and histology of 398 cases of patients with glioblastoma, who all underwent surgery in a regional Neurosurgical centre between April 2012 and December 2014. Mutated IDH was assessed by immunohistochemistry for the most common R132h mutant. Tissue factor expression was detected by immunohistochemistry. DVT and pulmonary embolism were diagnosed by Doppler ultrasound and pulmonary CT angiogram respectively in clinically relevant cases (no routine screening). We examined the Cancer Genome Atlas dataset for gene expression levels in GBM patients. Comparison was made of the expression level of the pro-coagulant thromboplastin (F3) gene between patients with WT and mutant IDH1.

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). WT IDH GBM patients express significantly higher levels of thromboplastin, a potential mechanism for the clinical observation. As expected, mutant IDH was associated with prolonged patient survival (p=0.024 Log rank). There was no difference in survival or age in patients with / without VTE (p=0.185 Log rank and p=0.733 T-test respectively).

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 in this at risk group.