title: High expression of the urokinase plasminogen activator and its cognate receptor associates with advanced stages and reduced disease-free interval in papillary thyroid carcinoma.
abstract: BACKGROUND
  The urokinase plasminogen activating system is implicated in neoplastic progression, and high tissue levels of urokinase plasminogen activating system components correlate with poor prognosis in various human cancers.
  
  
  OBJECTIVE
  The objective of the study was to investigate the prognostic relevance of the urokinase plasminogen activator (uPA), its cognate receptor (uPAR), and the plasminogen activator inhibitor 1 (PAI-1) in human papillary thyroid cancer (PTC).
  
  
  METHODS
  The expression of uPA, uPAR, and PAI-1 genes was analyzed in PTC and normal matched tissues by quantitative RT-PCR. The case study consisted of 99 patients (21 males and 78 females) affected by PTC including 77 classical, 15 follicular, four tall cell, and three oncocytic variants. Forty-one patients had lymph node metastases at the time of diagnosis. All the patients underwent thyroidectomy and radioiodine therapy followed by thyroid hormone replacement therapy. Follow-up data were available for 76 patients up to 64 months.
  
  
  RESULTS
  The uPA, uPAR, and PAI-1 mRNA levels were significantly higher in PTC compared with normal matched tissues by 9.63 ± 1,29-, 4.82 ± 0.45-, and 5.64 ± 0.71-fold, respectively. The increased expression of uPA and uPAR correlated statistically with advanced pT and N status. The uPA was also significantly associated with advanced tumor node metastasis stages. The Kaplan-Meier analysis showed a significant association of uPA and uPAR levels with reduced patient disease-free interval (DFI), and this association was stronger in stage I patients.
  
  
  CONCLUSIONS
  The study demonstrated that in PTC the increased gene expression of uPA and uPAR is associated with tumor invasiveness, advanced stages, and shorter DFI, suggesting their prognostic relevance. These observations warrant further investigation in larger patient populations with longer follow-up.
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Viale del Policlinico, 155, 00161 Roma, Italy. salvatore.ulisse@uniroma1.it
authors.forename: Salvatore
authors.initials: S
authors.lastname: Ulisse
authors.forename: Enke
authors.initials: E
authors.lastname: Baldini
authors.forename: Salvatore
authors.initials: S
authors.lastname: Sorrenti
authors.forename: Susi
authors.initials: S
authors.lastname: Barollo
authors.forename: Lucio
authors.initials: L
authors.lastname: Gnessi
authors.forename: Antonio
authors.initials: A
authors.lastname: Catania
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Pellizzo
authors.forename: Francesco
authors.initials: F
authors.lastname: Nardi
authors.forename: Caterina
authors.initials: C
authors.lastname: Mian
authors.forename: Enrico
authors.initials: E
authors.lastname: De Antoni
authors.forename: Massimino
authors.initials: M
authors.lastname: D'Armiento
authors.forename: Luigi
authors.initials: L
authors.lastname: Frati
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002648:Child; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis / Q000378:metabolism; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D055293:Receptors, Urokinase Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013965:Thyroidectomy; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator