title: Predicting outcomes of patients with intracranial meningiomas using molecular markers of hypoxia, vascularity, and proliferation.
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.
  
  
  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.
authors.affiliation: Department of Neurosurgery, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA. randy.jensen@hsc.utah.edu
authors.forename: Randy
authors.initials: R
authors.lastname: Jensen
authors.forename: Janet
authors.initials: J
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000378:metabolism; D049109:Cell Proliferation; D016009:Chi-Square Distribution; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008577:Meningeal Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D008579:Meningioma / Q000175:diagnosis* / Q000378:metabolism*; D008875:Middle Aged; D011237:Predictive Value of Tests; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D051272:Glucose Transporter Type 1; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019394:Ki-67 Antigen; D042461:Vascular Endothelial Growth Factor A; D005169:Factor VIII; C513496:MIB1 ligase, human; D044767:Ubiquitin-Protein Ligases; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases