Clinicopathological study of IDH1 mutation in high grade glioma patients in Hong Kong

Abstract

INTRODUCTION: The isocitrate dehydrogenase 1 (IDH1) gene is frequently mutated on amino acid residue R132H in certain subtypes of gliomas. IDH1 mutated gliomas are histologically indistinguishable from its wild type counterpart, however it displays a distinct clinical behavior and may be used to discriminate patients with more favorable prognosis and responses to chemotherapy. MATERIAL AND METHOD: To elucidate the incidence of IDH1 mutation and its clinical significance in high grade gliomas, IDH1 mutation status will be assessed by DNA sequencing and immunohistochemistry in a series of 50 high grade gliomas and the results will be correlated with age, gender, MGMT promoter methylation status, chemotherapy and overall survival. Subgroups of patients with and without methylated MGMT will be studied separately, and the response to temozolomide will be evaluated by progression free survival (PFS) and correlated with IDH1 mutation status. RESULTS AND CONCLUSION: The current study is ongoing and the anticipated results are that IDH1 mutations are associated with age and survival. Patients harboring IDH1 mutations generally have a younger median age and a relatively longer survival, and this correlation is independent of MGMT methylation status. It is also expected that IDH1 mutated tumors have better response to chemotherapy based on the PFS data. Similar studies conducted in other countries have indicated the great prognostic relevance of IDH1 mutation in gliomas. We review for the first time IDH1 mutation status of high grade gliomas in Hong Kong patients. This study may provide evidence to establish a more accurate assessment of response to temozolomide in addition to MGMT. Its detection could be incorporated into current pathology practice in order to guide clinicians of distinct treatment strategies.