High expression of the urokinase plasminogen activator and its cognate receptor associates with advanced stages and reduced disease-free interval in papillary thyroid carcinoma

Salvatore Ulisse, Enke Baldini, Salvatore Sorrenti, Susi Barollo, Lucio Gnessi, Antonio Catania, Maria Rosa Pellizzo, Francesco Nardi, Caterina Mian, Enrico De Antoni, Massimino D'Armiento, Luigi Frati

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Abstract

Context: 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). Design: 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)504-508
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Volume96
Issue number2
DOIs
Publication statusPublished - Feb 2011

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ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Ulisse, S., Baldini, E., Sorrenti, S., Barollo, S., Gnessi, L., Catania, A., Pellizzo, M. R., Nardi, F., Mian, C., De Antoni, E., D'Armiento, M., & Frati, L. (2011). High expression of the urokinase plasminogen activator and its cognate receptor associates with advanced stages and reduced disease-free interval in papillary thyroid carcinoma. Journal of Clinical Endocrinology and Metabolism, 96(2), 504-508. https://doi.org/10.1210/jc.2010-1688