PAI-1 and EGFR expression in adult glioma tumors: toward a molecular prognostic classification.
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.
Muracciole
Xavier
X
Department of Radiothérapie, CHU, La Timone, France.
Romain
Sylvie
S
Dufour
Henri
H
Palmari
Jacqueline
J
Chinot
Olivier
O
Ouafik
L'Houcine
L
Grisoli
Francois
F
Branger
Dominique Figarella
DF
Martin
Pierre Marie
PM
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
D009363:Neoplasm Proteins; D017395:Plasminogen Activator Inhibitor 1; D066246:ErbB Receptors