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

Jensen, Randy MD, PhD; Lee, Janet MD, MS, MPH

doi: 10.1227/NEU.0b013e3182567886
CNS University of Neurosurgery

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.

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.

ABBREVIATIONS: CA-IX, carbonic anhydrase-IX

Glut-1, glucose transporter-1

HIF-1α, hypoxia-inducible factor-1α

MVD, microvascular density

OS, overall survival

PFS, progression-free survival

PI, proliferation index

PTBE, peritumoral brain edema

VEGF, vascular endothelial growth factor

WHO, World Health Organization

Department of Neurosurgery, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah

Correspondence: Randy L. Jensen, MD, PhD, Department of Neurosurgery, University of Utah, 175 N. Medical Dr East, Salt Lake City, UT 84132. E-mail:

Received September 28, 2011

Accepted March 2, 2012

Copyright © by the Congress of Neurological Surgeons