Diagnostic and prognostic implications of molecular status in Chinese adults with diffuse glioma: An observational study

Background and Aim: Mutations in isocitrate dehydrogenase (IDH), co-deletion of 1p and 19q, loss or expression of the transcription regulator ATRX, and mutations in telomerase reverse transcriptase (TERT) gene promoters are intimately linked with diffuse gliomas. We further explored the roles of the key molecules in adulthood diffuse gliomas and their prognosis. Materials and Methods: A total of 413 patients who underwent primary surgery between 2009 and 2015 at Xuanwu Hospital, Beijing, China, were included in this observational study. All specimens from the patients were fixed in 10% neutral buffered formalin and embedded in paraffin. The mutational status of IDH1/2 and the TERT promoter was determined using polymerase chain reaction-based direct sequencing. The assay for the 1p and 19q co-deletion was conducted using fluorescence in situ hybridization. Overall- and progression-free survival was calculated using the Kaplan-Meier method and the log-rank test. The study was approved by the Ethics Committee of Xuanwu Hospital, Capital Medical University, China (approval No. [2019]004) on May 22, 2019. Results: We found that tumors characterized by multiple lesions were predominantly free of IDH mutations (P < 0.001). Gliomas with IDH mutations arose more often in the frontal and insular lobes than in the other lobes (P < 0.001). Rates of IDH mutations were higher in patients who had seizures or were without discomfort than in those who had other clinical symptoms (P = 0.0003). Of 119 patients with complete molecular information according to the 2016 World Health Organization classification of central nervous system tumors, 5 had oligoastrocytomas that had multiple genotypes - IDH1 mutation, loss of ATRX expression, and 1p/19q co-deletion - but lacked TERT promoter mutations. Patients with seizures or without discomfort who had IDH mutations had better outcomes than did other patients (P < 0.001). Patients whose tumors had IDH and TERT promoter mutations had a better prognosis than did other patients (P < 0.001). Among patients whose tumors had wild-type IDH, those with loss of ATRX survived longer than did others (P = 0.005). Conclusions: The status of both ATRX and the TERT promoter can indicate the prognosis in patients with IDH wild-type gliomas. The diagnosis that is based on clinical symptoms, histologic findings, and molecular analysis should be implemented as the diagnostic standard for patients with oligoastrocytomas.