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Urokinase Plasminogen Activator and Its Inhibitor Type-I as Prognostic Factors in Differentiated Thyroid Carcinoma Patients

Objective was to investigate the prognostic value of urokinase-type plasminogen activator (uPA) and its inhibitor, type-I plasminogen activator inhibitor (PAI-I), in differentiated thyroid cancer. Cytosolic concentrations of uPA and PAI-I were determined in 105 patients with differentiated thyroid carcinoma and normal matched tissues using an enzyme-linked immunoassay (ELISA). Both uPA and PAI-I concentrations were significantly higher in differentiated thyroid tumors (uPA=0, 509±0, 767 and PAI-I = 6, 337±6, 415 ng/mg) compared to normal tissues (uPA=0, 237±0, 051, P < , 015, PAI-I, P < , 001). uPA and PAI-I were significantly higher if extrathyroidal invasion (uPA, P = , 015: PAI-I, P< , 001) or distant metastasis (PAI-I p< , 001) was present, as well as in tumors whose size exceeded 1 cm in diameter (uPA, p 0 , 002 ; PAI-I, P = , 001). Survival analysis revealed the significant impact of both uPA and PAI-I 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-I, respectively, P < , 001). Univariate analysis showed that gender, tumor size, tumor grade, extrathyroid invasion, local lymph node involvement, distant metastases, uPA, and PAI-I were significant predictors of PFS. However, multivariate analysis identified only distant metastases and tumor tissue uPA and PAI-I as independent prognostic factors. These findings indicate that high uPA an PAI-I levels represent independent unfavorable prognostic factors in patients with differentiated thyroid carcinoma.

Urokinase-type plasminogen activator; type-I plasminogen activator inhibitor; differentiated thyroid carcinoma; prognosis; enzyme-linked immunosorbent assay

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