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: firstname.lastname@example.org
Received September 28, 2011
Accepted March 2, 2012