Urokinase plasminogen activator and its inhibitor type-1 as prognostic factors in differentiated thyroid carcinoma patients.

Abstract

To investigate the prognostic value of urokinase-type plasminogen activator (uPA) and its inhibitor, type-1 plasminogen activator inhibitor (PAI-1), in differentiated thyroid cancer. Prospective cohort study. University hospital. Cytosolic concentrations of uPA and PAI-1 were determined in 105 patients with differentiated thyroid carcinoma and normal matched tissues using an enzyme-linked immunoassay (ELISA). Both uPA and PAI-1 concentrations were significantly higher in differentiated thyroid tumors (uPA = 0.509 ± 0.767 and PAI-1 = 6.337 ± 6.415 ng/mg) compared to normal tissues (uPA = 0.237 ± 0.051, P < .001; PAI-1 = 2.368 ± 0.418 ng/mg, P < .001). uPA and PAI-1 were significantly higher if extrathyroidal invasion (uPA, P = .015; PAI-1, P < .001) or distant metastasis (PAI-1 P < .001) was present, as well as in tumors whose size exceeded 1 cm in diameter (uPA, P = .002; PAI-1, P = .001). Survival analysis revealed the significant impact of both uPA and PAI-1 on progression-free survival (PFS) (82.22 vs 49.478 months for patients with low and high uPA, respectively, P < .001; 87.068 vs 44.964 months for patients with low and high PAI-1, respectively, P < .001). Univariate analysis showed that gender, tumor size, tumor grade, extrathyroid invasion, local lymph node involvement, distant metastasis, uPA, and PAI-1 were significant predictors of PFS. However, multivariate analysis identified only distant metastasis and tumor tissue uPA and PAI-1 as independent prognostic factors. These findings indicate that high uPA and PAI-1 levels represent independent unfavorable prognostic factors in patients with differentiated thyroid carcinoma.