title: Urokinase plasminogen activator and its inhibitor type-1 as prognostic factors in differentiated thyroid carcinoma patients.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Prospective cohort study.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These findings indicate that high uPA and PAI-1 levels represent independent unfavorable prognostic factors in patients with differentiated thyroid carcinoma.
authors.affiliation: Department of Nuclear Medicine and Radiation Protection, University Hospital Center Zagreb, Zagreb, Croatia.
authors.forename: Gordana
authors.initials: G
authors.lastname: Horvatic Herceg
authors.forename: Davorin
authors.initials: D
authors.lastname: Herceg
authors.forename: Marko
authors.initials: M
authors.lastname: Kralik
authors.forename: Ana
authors.initials: A
authors.lastname: Kulic
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Bence-Zigman
authors.forename: Hrvojka
authors.initials: H
authors.lastname: Tomic-Brzac
authors.forename: Irena
authors.initials: I
authors.lastname: Bracic
authors.forename: Sanja
authors.initials: S
authors.lastname: Kusacic-Kuna
authors.forename: Drago
authors.initials: D
authors.lastname: Prgomet
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D017395:Plasminogen Activator Inhibitor 1; D011379:Prognosis; D011446:Prospective Studies; D013964:Thyroid Neoplasms / Q000201:enzymology* / Q000401:mortality* / Q000473:pathology; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors; D055815:Young Adult
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D014568:Urokinase-Type Plasminogen Activator
keywords: differentiated thyroid carcinoma; enzyme-linked immunosorbent assay; prognosis; type-1 plasminogen activator inhibitor; urokinase-type plasminogen activator