Assessment of Isocitrate Dehydrogenase 1 Mutation by Immunohistochemistry in Egyptian Patients with High-grade Gliomas

Abstract

BACKGROUND: At present, the classification of central nervous system tumors relies on molecular factors in addition to histologic features to identify many tumor types. This should subsequently results in more accurate diagnosis as well as addressing specific markers of potential prognostic and predictive value. AIM: This study was conducted to emphasize the importance of including isocitrate dehydrogenase 1 (IDH1) evaluation as a crucial part of the diagnosis and categorization of high-grade glioma cases. This also may help to individualize the treatment of high-grade glioma patients. MATERIALS AND METHODS: The current study included 60 cases of high-grade gliomas, studied histologically and immunohistochemically for the detection of IDH1 mutation. The results were correlated with different clinicopathologic variables and course of the disease. RESULTS: IDH1 immunohistochemical expression was positive in 46.67% of the studied high-grade glioma cases. A statistically significant relationship was detected between IDH1 expression and tumor histologic grade as 100% of Grade III anaplastic oligodendroglioma cases and 80% of the Grade III anaplastic astrocytoma cases were IDH1 positive while only 40.4% of Grade IV glioblastoma cases were IDH1 positive (p = 0.03). In addition, patients who were IDH1 mutant were in a better category of response to radiotherapy (p = 0.019) and also to chemotherapy (p < 0.001). Moreover, patients who expressed IDH1 had prolonged overall survival (OS) and progression-free survival than those who showed negative IDH1expression (p < 0.001). On the other hand, no statistically significant relationship was detected between IDH1 expression and patients age, sex, tumor site, tumor size, motor symptoms, sensory symptoms, and increased intracranial tension (p > 0.05). CONCLUSIONS: It is suggested that IDH1 is a good prognostic marker for gliomas and is a good predictive marker for response to treatment. IDH1 is a promising target for therapy in high-grade gliomas through the emerging IDH1 inhibitors. Immunohistochemical testing for IDH1 is a practical and cost-effective method that should be applied in all glioma cases. Further study on a larger sample size is recommended to validate the current results. Moreover, applying molecular analysis to detect IDH1 mutation is recommended to be able to precisely detect the IDH1 wild-type tumor