Urokinase receptor forms in serum from non-small cell lung cancer patients: Relation to prognosis.

10518 Background: The plasminogen activation system is involved in extracellular proteolysis during cancer invasion. In addition to the generation of plasminogen, urokinase (uPA) can cleave its cellular three-domain receptor, uPAR(I-III), between domain I and II, liberating domain I, uPAR(I), and leaving uPAR(II-III) on the cell surface. Both uPAR(I-III) and uPAR(II-III) can be shed from the cell. Recently, we found that high levels of both intact uPAR and its cleaved forms in blood from a small number (n = 32) of patients operated for non-small cell lung cancer (NSCLC) were associated with short overall survival (OS). The aim of the study was to investigate the prognostic impact of uPAR forms in serum from 171 NSCLC patients. Methods: Serum sampled preoperatively was available from 171 patients radically resected for NSCLC. uPAR(I-III), uPAR(I-III) plus uPAR(II-III) and uPAR(I) were measured by time-resolved fluoroimmunoassays. Results: High serum levels of each of the three uPAR forms were associated with short OS. In a multivariate survival analysis uPAR(l-lll) and uPAR(l) remained significant prognostic parameters independently of stage, histology, age, performance status and therapy, uPAR(l-lll) being the strongest (hazard ratio [HR] = 2.3, confidence interval [CI]: 1.2-4.5, p = 0.015). Conclusions: This retrospective study validate a previous study and shows that uPAR(l-lll) and uPAR(l) in serum are independent prognostic factors in patients radically operated for NSCLC. No significant financial relationships to disclose.