Predicting Outcomes of Patients With Intracranial Meningiomas Using Molecular Markers of Hypoxia, Vascularity, and Proliferation

BACKGROUND: The natural history of surgically treated intracranial meningiomas can be quite variable. Recurrence and patient outcome cannot currently be predicted with accuracy. OBJECTIVE: To explore the potential roles of tumor hypoxia-regulated biological markers, preoperative imaging, measures of proliferation, and angiogenesis in predicting patient outcome. METHODS: Tissue from 263 patients (average follow-up, 75 months) was examined for molecular markers hypoxia-inducible factor-1 alpha (HIF-1 alpha), carbonic anhydrase-IX (CA-IX), and glucose transporter-1 (Glut-1); vascular endothelial growth factor (VEGF); proliferation (MIB-1); and microvascular density (MVD) (Factor VIII). Preoperative magnetic resonance images were also examined for tumor size and peritumoral brain edema (PTBE). RESULTS: VEGF, HIF-1 alpha, CA-IX, and Glut-1 are positively correlated (P < .001-.005). PTBE was associated with higher grade (P = .03), larger tumors (P = .02), and log of MVD (P = .004). Progression-free survival (PFS) was associated with higher grade (P < .001), subtotal resection (P = .004), VEGF expression (P = .004), and log of MIB-labeling index (P < .001) on pairwise comparisons. Using multivariate analysis, PFS was associated with subtotal resection (HR 2.71, P = .027), higher grade (HR 6.29, P < .001), higher VEGF expression (HR 1.52, P = .038), and log of MIB-labeling index (HR 1.68, P = .005). Shorter overall survival was associated with subtotal resection (HR 3.23, P = .002), higher grade (HR 4.47, P < .001), higher expression of HIF-1 alpha (HR 1.56, P < .001) and Glut-1 (HR 1.39, P = .02), and log of MIB-labeling index (HR 1.87, P < .001) when controlled for age. CONCLUSION: HIF, VEGF, and MIB-1 are significantly correlated with tumor recurrence. With further study, these molecular markers may be used to predict outcome for patients with intracranial meningiomas.