IBRO Neuroscience Reports (Dec 2022)
Impact of new molecular criteria on diagnosis and survival of adult glioma patients
Abstract
The fifth edition WHO classification of Tumors of the Central nervous system (WHO-CNS5) integrated new molecular parameters to refine CNS tumor classification. This study aimed to reclassify a retrospective cohort of adult glioma patients according to WHO-CNS5, and assess if overall survival (OS) correlated with the revised diagnosis. Further, the diagnostic impact of methylation profiling (MP) was evaluated. Adult gliomas diagnosed according to 2016 WHO-CNS (n = 226) were evaluated according to WHO-CNS5 criteria. All patients had diagnostic NGS performed. 29 patients had 850k MP performed due to challenging tumor cases. OS was analyzed using Kaplan-Meier plots and log-rank test. 19 patients were reclassified. Specifically, diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma (DAG-G) were reclassified as glioblastoma (n = 15). Shifts to glioblastoma were because of TERT promoter (TERTp) mutation (n = 9), EGFR amplification (n = 2), EGFR amplification and TERTp mutation (n = 1), and TERTp mutation with gain of chromosome 7, but uncertain chromosome 10 status due to lack of NGS coverage (n = 3). Lower grade IDH-mutant astrocytomas were reclassified as astrocytoma IDH-mutant, WHO grade 4 due to CDKN2A/B homozygous deletion (n = 4). No significant difference in OS was found for reclassified DAG-G in whole group (p = 0.59) and for TERTp mutation only (p = 0.44), compared to glioblastoma. MP resulted in revised diagnosis (n = 2), confirmed diagnosis (n = 15) and no match (n = 12). Our study showed similar overall survival for glioblastoma and DAG patients, supporting that isolated TERTp mutation may have a prognostic role in IDH-wildtype gliomas. Further, our study suggests MP is useful for confirming the diagnoses in challenging tumors.