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-1α (HIF-1α), 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-1α, 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-1α (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.

CONCLUSIONS

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.