title: PAI-1 and EGFR expression in adult glioma tumors: toward a molecular prognostic classification.
abstract: OBJECTIVE
  Molecular classification of gliomas is a major challenge in the effort to improve therapeutic decisions. The plasminogen activator system, including plasminogen activator inhibitor type 1 (PAI-1), plays a key role in tumor invasion and neoangiogenesis. Epidermal growth factor receptor (EGFR) is involved in the control of proliferation. The contribution of PAI-1 and EGFR to the survival of gliomas was retrospectively investigated.
  
  
  METHODS
  Fifty-nine adult gliomas treated by neurosurgery and conventional irradiation were analyzed, including 9 low-grade (2) and 50 high-grade (3-4) tumors (WHO classification). PAI-1 was measured on cytosols and EGFR on solubilized membranes using ELISA methods.
  
  
  RESULTS
  High PAI-1 levels were strongly associated with high histologic grade (p < 0.001) and histologic necrosis (p < 0.001). PAI-1 also correlated positively with patient age (p = 0.05) and negatively with Karnofsky index (p = 0.01). By univariate analysis of the high-grade population, higher PAI-1 (p < 0.0001) and EGFR values (p = 0.02) were associated with shorter overall survival. Only PAI-1 was an independent factor in multivariate analysis. Grade 3 tumors with low PAI-1 (100% 3-year overall survival rate) presented the same clinical outcome as the low-grade tumors.
  
  
  CONCLUSIONS
  In this prognostic study, PAI-1 and EGFR expression revealed similarities and differences between high-grade gliomas that were not apparent by traditional clinical criteria. These data strongly support that biologic factors should be included in glioma classification and the design of clinical trials to treat more homogeneous populations.
authors.affiliation: Department of Radiothérapie, CHU, La Timone, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Muracciole
authors.forename: Sylvie
authors.initials: S
authors.lastname: Romain
authors.forename: Henri
authors.initials: H
authors.lastname: Dufour
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Palmari
authors.forename: Olivier
authors.initials: O
authors.lastname: Chinot
authors.forename: L'Houcine
authors.initials: L
authors.lastname: Ouafik
authors.forename: Francois
authors.initials: F
authors.lastname: Grisoli
authors.forename: Dominique Figarella
authors.initials: DF
authors.lastname: Branger
authors.forename: Pierre Marie
authors.initials: PM
authors.lastname: Martin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001932:Brain Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D066246:ErbB Receptors / Q000032:analysis*; D005910:Glioma / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D006801:Humans; D017567:Karnofsky Performance Status; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis*; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D009363:Neoplasm Proteins; D017395:Plasminogen Activator Inhibitor 1; D066246:ErbB Receptors