Artikel
Expression of uPA and PAI-1 in meningiomas correlates with malignant progression and brain invasion
uPA- und PAI-1-Expression in Meningeomen korreliert mit maligner Progression und Hirninvasion
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Autoren
Veröffentlicht: | 4. Mai 2005 |
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Gliederung
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Objective
Brain invasion often causes meningioma recurrence. Brain invasion has been regarded as a decisive (histopathological) parameter for the diagnosis of malignancy in meningiomas. Multiple meningiomas are often of monoclonal origin possibly reflecting subarachnoid spread. Invasion and metastatic spread require the proteolytic degradation of the extracellular matrix, which is mediated, in part, by activation of uPA (urokinase-type plasminogen activator) and its inhibitor PAI-1 (plasminogen activator inhibitor-1). In this study we investigate the role of uPA and PAI-1 in meningiomas.
Methods
uPA and PAI-1 protein concentrations were determined in shock-frozen tissue of 26 benign WHO grade I, 17 atypical WHO grade II and 6 anaplastic/malignant WHO grade III meningiomas using an ELISA assay.
Results
Expression of uPA increased significantly with the WHO grade (WHO grade I: 0.247±0.035, WHO grade II: 0.420±0.066, WHO grade III: 1.108±0.736 ng/mg; p<0.05, H test). High levels of PAI-1 were observed primarily in malignant/anaplastic meningiomas (WHO grade I/II: 7.5±1.0, WHO grade III: 237.0±112.3; p<0.025, U test). Expression of PAI-1 correlated significantly with brain invasion (120.3±73.0 vs. 21.5±14.8; p<0.005, U test). High levels of uPA and PAI-1 protein were often seen independently. Tumor multiplicity (>3 tumors) corrrelated neither with uPA nor with PAI-1 expression.
Conclusions
The molecular biology of invasion and (metastatic) subarachnoid spread of meningiomas has not been very well researched. Activation of the plasmin/uPA/PAI-1 system might play a significant role during the malignant progression of meningiomas and meningioma brain invasion. Differential expression of high levels of uPA and PAI-1 protein argues for at least partially independent functions of these proteins in meningiomas. Finally, PAI-1 and uPA could prove useful for meningioma grading. High levels of uPA and PAI expression are already in clinical use as negative prognostic factors in several (mainly gynecological) malignancies.