Predicting outcomes of patients with intracranial meningiomas using molecular markers of hypoxia, vascularity, and proliferation

Neurosurgery. 2012 Jul;71(1):146-56. doi: 10.1227/NEU.0b013e3182567886.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / metabolism
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases / metabolism
  • Cell Proliferation*
  • Chi-Square Distribution
  • Factor VIII / metabolism
  • Female
  • Gene Expression Regulation / physiology
  • Glucose Transporter Type 1 / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Ki-67 Antigen / metabolism
  • Logistic Models
  • Magnetic Resonance Imaging
  • Male
  • Meningeal Neoplasms / diagnosis*
  • Meningeal Neoplasms / metabolism*
  • Meningioma / diagnosis*
  • Meningioma / metabolism*
  • Middle Aged
  • Predictive Value of Tests
  • Ubiquitin-Protein Ligases / metabolism
  • Vascular Endothelial Growth Factor A / metabolism
  • Young Adult

Substances

  • Antigens, Neoplasm
  • Glucose Transporter Type 1
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Ki-67 Antigen
  • Vascular Endothelial Growth Factor A
  • Factor VIII
  • MIB1 ligase, human
  • Ubiquitin-Protein Ligases
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases