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Aims: We aimed to reclassify a population‐based cohort of 529 adult glioma patients to evaluate the prognostic impact of the 2016 World Health Organization (WHO) central nervous system tumour classification. Moreover, we evaluated the feasibility of gene panel next‐generation sequencing (NGS) in daily diagnostics of 225 prospective glioma patients. Methods: The retrospective cohort was reclassified according to WHO 2016 criteria by immunohistochemistry for IDH‐R132H, fluorescence in situ hybridization for 1p/19q‐codeletion and gene panel NGS. All tumours of the prospective cohort were subjected to NGS analysis up‐front. Results: The entire population‐based cohort was successfully reclassified according to WHO 2016 criteria. NGS results were obtained for 98% of the prospective patients. Survival analyses in the population‐based cohort confirmed three major prognostic subgroups, that is, isocitrate dehydrogenase (IDH)‐mutant and 1p/19q‐codeleted oligodendrogliomas, IDH‐mutant astrocytomas and IDH‐wildtype glioblastomas. The distinction between WHO grade II and III was prognostic in patients with IDH‐mutant astrocytoma. The survival of patients with IDH‐wildtype diffuse astrocytomas carrying TERT promoter mutation and/or EGFR amplification overlapped with the poor survival of IDH‐wildtype glioblastoma patients. Conclusions: Gene panel NGS proved feasible in daily diagnostics. In addition, our study confirms the prognostic role of glioma classification according to WHO 2016 in a large population‐based cohort. Molecular features of glioblastoma in IDH‐wildtype diffuse glioma were linked to poor survival corresponding to IDH‐wildtype glioblastoma patients. The distinction between WHO grade II and III retained prognostic significance in patients with IDH‐mutant diffuse astrocytic gliomas. [ABSTRACT FROM AUTHOR] more...

Aims: Glioblastomas are highly aggressive and treatment resistant. Increasing evidence suggests that tumour‐associated macrophages/microglia (TAMs) facilitate tumour progression by acquiring a M2‐like phenotype. Our objective was to investigate the prognostic value of TAMs in gliomas using automated quantitative double immunofluorescence. Methods: Samples from 240 patients with primary glioma were stained with antibodies against ionized calcium‐binding adaptor molecule‐1 (IBA‐1) and cluster of differentiation 204 (CD204) to detect TAMs and M2‐like TAMs. The expression levels were quantified by software‐based classifiers. The associations between TAMs, gemistocytic cells and glioblastoma subtype were examined with immuno‐ and haematoxylin–eosin stainings. Three tissue arrays containing glioblastoma specimens were included to study IBA‐1/CD204 levels in central tumour and tumour periphery and to characterize CD204+ cells. Results: Our data revealed that the amount of especially CD204+ TAMs increases with malignancy grade. In grade III–IV, high CD204 expression was associated with shorter survival, while high IBA‐1 intensity correlated with a longer survival. In grade IV, CD204 showed independent prognostic value when adjusting for clinical data and the methylation status of O6‐methylguanine–DNA methyltransferase. Our findings were confirmed in two bioinformatics databases. TAMs were more abundant in central tumour tissue, mesenchymal glioblastomas and gliomas with many gemistocytic cells. CD204+ TAMs co‐expressed proteins related to tumour aggressiveness including matrix metallopeptidase‐14 and hypoxia‐inducible factor‐1α. Conclusions: This is the first study to use automated quantitative immunofluorescence to determine the prognostic impact of TAMs. Our results suggest that M2‐like TAMs hold an unfavourable prognostic value in high‐grade gliomas and may contribute to a pro‐tumourigenic microenvironment. [ABSTRACT FROM AUTHOR] more...