Meningioma grade and molecular markers of proliferation, hypoxia, and vascularity as predictors of outcome in a cohort with long-term patient follow-up.

Purpose: To identify clinical, pathologic, and imaging predictors of progression and survival in intracranial meningioma using the 2021 World Health Organization (WHO) grading system with long-term follow-up.

Methods: We retrospectively analyzed 132 patients (143 tumors) resected from 1991 to 2011 and regraded tumors per WHO 2021 criteria. Outcomes were progression-free survival (PFS) and overall survival (OS). Immunohistochemical markers from archival tissue included proliferation (MIB-1), hypoxia (GLUT-1, HIF-1α, CA-IX), angiogenesis (VEGF), and vascularity (microvascular density [MVD]) with prespecified thresholds. Preoperative tumor and peritumoral brain edema (PTBE) volumes were segmented to calculate a PTBE ratio (edema: tumor). Cox models evaluated covariates (PFS: WHO 2021 grade 2, MIB-1 > 5%, PTBE ratio; OS: subtotal vs. gross total resection, WHO 2021 grade 2).

Results: Median follow-up was 17.1 years. PFS was independently associated with WHO 2021 grade 2 (HR 3.72, 95% CI 1.49-9.32), MIB-1 > 5% (HR 2.56, 95% CI 1.17-5.60), and PTBE ratio (HR 1.22 per 0.1 increment, 95% CI 1.04-1.43). OS was associated with subtotal resection (HR 2.69, 95% CI 1.28-5.65) and WHO 2021 grade 2 (HR 4.27, 95% CI 1.61-11.33). Hypoxia/angiogenesis markers were not significant in multivariable models. Median PFS was not reached; 3- and 5-year estimates were 84.1% and 79.6%.

Conclusions: With WHO 2021 regrading and extended follow-up, grade, MIB-1, and PTBE stratify PFS, whereas extent of resection and grade predict OS. These accessible factors may guide counseling and surveillance where molecular profiling is unavailable.