engleski

Impact of Urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) on progression-free survival in thyroid cancer

Purpose: Higher levels of urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) are linked to the poor prognosis in a variety of malignances. uPA and PAI-1 were expressed in most thyroid carcinomas, as had been measured immunohistochemically. However, no relationship between their expression and clinicopathological parameters were described. Aim of the present study was to investigate the expression and clinical relevance of uPA and PAI-1 in thyroid cancer. Patients and methods: uPA and PAI-1 in paired cytosol samples of thyroid tumor and normal tissue were determined in 23 patients using enzyme-linked immunosorbent assay and correlated to the known prognostic features. Results: Both uPA and PAI-1 concentrations were significantly higher in malignant thyroid tumors (uPA=1.342&#177; ; 2.944 and PAI-1=17.615&#177; ; 31.933 ng/mg protein) than in normal tissue (uPA=0.002&#177; ; 0.009, P=0, 011 and PAI-1=2.333&#177; ; 0.338 ng/mg protein, P=0, 001) with positive correlation of the two proteins in the tumors. uPA and PAI-1 were significantly higher in anaplastic vs. well-differentiated cancers (uPA P=0.014 and PAI-1 P=0.026), if extrathyroidal invasion (uPA P=0.019 and PAI-1 P=0.009) or distant metastases (uPA P=0.006 and PAI-1 P=0.003) had been present, and in tumors whose size exceeded 1 cm in diameter (uPA P=0.009 and PAI-1 P=0.035). Only PAI-1, but not uPA was significantly higher in multicentric vs. solitary tumors (P=0.012) and lymph node positive compared to lymph node negative patients (P=0.042). The differences of uPA and PAI-1 did not reach the significant level when patients with well-differentiated tumors below and above 40 years of age had been compared. Survival analysis revealed the significant impact of both uPA and PAI-1 on the Progression-Free Survival (PFS) (38.84 vs. 3.67 months for patients with low and high uPA, respectively, P<0.001 ; 38.2 vs. 12 months for patients with low and high PAI-1, respectively, P=0.016). Conclusions: The correlation of high uPA and PAI-1 with the known prognostic factors of poorer outcome and with lower PFS rate in patients with thyroid cancers proved that these proteins could be an additional prognostic parameter.

plasminogen activation system; thyroid cancer; progression free survival

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