Abstract
BACKGROUND: The 2021 WHO classification has standardized the categorization of grade 2/3 gliomas into oligodendroglioma (Oligo) and astrocytoma (Astro). However, the prognostic impact of histological grading and treatment outcome differences remain unclear. METHODS: A multicenter retrospective study was conducted using 2,059 cases that underwent surgery between 2000 and 2019 across 20 institutions in Japan. Among these, 503 Oligo and 436 Astro cases with confirmed IDH1/2 mutation and 1p/19q codeletion status were analyzed. RESULTS: Histological grade 3 was associated with significantly lower 10-year survival rates compared to grade 2 in both Oligo (G2: 90.9%, G3: 73.8%) and Astro (G2: 66.6%, G3: 60.0%). IDH2 mutations were more frequent in Oligo than Astro (5.7% vs. 1.1%) and in grade 3 than grade 2 tumors (4.9% vs. 2.2%). CDKN2A/B homozygous deletion (HD) was observed at similar rates in Oligo and Astro (7.5% vs. 9.1%) but was more frequent in grade 3 than grade 2 tumors (13.4% vs. 4.3%). CDKN2A/B-HD was associated with worse prognosis in Astro but not in Oligo. Among Oligo cases (grades 2 and 3 combined), overall survival was not significantly affected by radiotherapy or chemotherapy type (ACNU-based, TMZ-based, or no chemotherapy). DISCUSSION: While molecular classification is the primary determinant, histological grading retains prognostic significance. Differences in IDH2 mutation and CDKN2A/B-HD frequencies were associated with histological grade. The potential influence of histological grade as a confounding factor in treatment outcomes warrants further investigation.