Determining IDH-Mutational Status in Gliomas Using IDH1-R132H Antibody and Polymerase Chain Reaction

Abstract

Determination of the isocitrate dehydrogenase (IDH) mutation status, presence or absence of mutation in IDH genes (IDH1 or IDH2), has become one of the most important molecular features taken into account in the management of patients with diffuse gliomas. Tumors that are IDH-mutant have a better prognosis than their counterparts with similar histologic grade and IDH-wildtype phenotype. IDH1-R132H is the most common IDH mutation, present in ~90% of IDH-mutant cases. This mutation yields an altered protein that can be detected by immunohistochemistry. We evaluated the IDH1-R132H antibody (clone H09) to determine IDH mutation status as the first line test and compared with the results of polymerase chain reaction (PCR) testing that can detect more types of mutations in IDH1 or IDH2. A total of 62 gliomas were evaluated: 30 glioblastomas (including 3 gliosarcomas), 11 grade III diffuse gliomas, 17 grade II diffuse gliomas, and 4 circumscribed gliomas. Twelve of 62 cases were IDH-mutant by immunohistochemistry and 15 of 62 by PCR. PCR detected the following mutations: IDH1-R132H (11 cases), IDH1-R132C (1 case), IDH2 R172, NOS (1 case), IDH1 R132, NOS (1 case), and IDH2-R172K (1 case). The R132H antibody had high specificity (100%) and sensitivity (80%) to detect IDH mutation status; the discordant results were 3 false-negatives. IDH-R132H immunostain is suitable as a first line test. Nonimmunoreactive cases could be studied by PCR following recommendations of the 2016 World Health Organization guidelines.