Prognostic impact of liberated domain I of the urokinase plasminogen activator receptor in squamous cell lung cancer tissue

Abstract

The purpose of this study was to determine the prognostic impact of liberated domain I of the urokinase plasminogen activator receptor, uPAR(I), in tumour extracts from patients resected for the squamous cell carcinoma (SCC) of the lung. A recently developed time-resolved fluoroimmunoassay for uPAR(I), TR-FIA 3, was validated using a pool of SCC tumour extracts. This assay was then used to measure the levels of uPAR(I) in tumour extracts from 63 SCC patients. Overall survival of the patients was measured from the day of surgical resection until death or until a review after a median of 144 months observation. The Cox proportional hazard model was used for uni- and multivariate survival analysis. TR-FIA 3 was found to measure uPAR(I) in SCC tumour extracts with high precision, accuracy and specificity. Univariate analysis using log transformed uPAR(I) concentrations showed that there was an increasing risk of mortality with increasing uPAR(I) levels in SCC tumour extracts, the hazard ratio (HR) being 2.9 with a P-value of 0.003. In a multivariate analysis, including uPAR(I), gender, age, nodal status, tumour size and levels of uPAR immunoreactivity measured by ELISA, statistically significant prognostic impact was found only for levels of uPAR(I) (HR 3.7, P=0.002) and tumour size (HR 2.4, P=0.02). uPAR(I) levels in the extracts of primary tumours independently predicted overall survival of 63 patients with SCC.