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http://purl.uniprot.org/citations/22702340http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22702340http://www.w3.org/2000/01/rdf-schema#comment"

Context

It has been suggested that patients with papillary thyroid cancer (PTC) harbouring the BRAF(V600E) mutation have a worse prognosis. We showed in PTC that high levels of urokinase plasminogen activator (uPA) and its cognate receptor (uPAR) inversely correlate with disease-free interval (DFI).

Objectives

To investigate the effects of BRAF(V600E) on the expression of uPA and uPAR and to evaluate the prognostic relevance of BRAF(V600E) alone or in combination with uPA and uPAR. DESIGN/SETTING/PATIENTS/INTERVENTION: The case study included 91 patients with PTC. All patients underwent thyroidectomy and radioiodine therapy. Follow-up was available for 75 patients.

Main outcome measures

The BRAF(V600E) mutation was analysed by sequencing and mutant allele-specific PCR amplification; uPA and uPAR expression by quantitative RT-PCR.

Results

BRAF(V600E) was found in 44 of the 91 patients and associated with older age, but not with high-risk clinicopathological features. Urokinase PA and uPAR mRNA levels were higher in tumour tissues by 9·51 ± 1·30 and 4·64 ± 0·44 fold, respectively, compared to normal matched tissues, being significantly higher in BRAF(V600E) -positive patients. In vitro induction of BRAF(V600E) in PCCL3 cells caused a significant increase in both uPA and uPAR mRNAs. Higher levels of uPA and uPAR correlated with lymph node metastases, TNM stage and disease recurrences. Kaplan-Meier and multivariate analyses demonstrated that uPA and uPAR were associated with shorter DFI, while the BRAF(V600E) was not.

Conclusion

In PTC, BRAF(V600E) induces uPA and uPAR expression. The latter, but not BRAF(V600E) , associates with advanced stages and shorter DFI. If confirmed in larger case studies, they may represent reliable prognostic markers for more accurate risk stratification and postoperative decision-making in patients with PTC."xsd:string
http://purl.uniprot.org/citations/22702340http://purl.org/dc/terms/identifier"doi:10.1111/j.1365-2265.2012.04465.x"xsd:string
http://purl.uniprot.org/citations/22702340http://purl.uniprot.org/core/author"Baldini E."xsd:string
http://purl.uniprot.org/citations/22702340http://purl.uniprot.org/core/author"D'Armiento M."xsd:string
http://purl.uniprot.org/citations/22702340http://purl.uniprot.org/core/author"Sorrenti S."xsd:string
http://purl.uniprot.org/citations/22702340http://purl.uniprot.org/core/author"Ulisse S."xsd:string
http://purl.uniprot.org/citations/22702340http://purl.uniprot.org/core/author"Catania A."xsd:string
http://purl.uniprot.org/citations/22702340http://purl.uniprot.org/core/author"Gnessi L."xsd:string
http://purl.uniprot.org/citations/22702340http://purl.uniprot.org/core/author"Palermo S."xsd:string
http://purl.uniprot.org/citations/22702340http://purl.uniprot.org/core/author"Mian C."xsd:string
http://purl.uniprot.org/citations/22702340http://purl.uniprot.org/core/author"Barollo S."xsd:string
http://purl.uniprot.org/citations/22702340http://purl.uniprot.org/core/author"Pelizzo M.R."xsd:string
http://purl.uniprot.org/citations/22702340http://purl.uniprot.org/core/author"De Antoni E."xsd:string
http://purl.uniprot.org/citations/22702340http://purl.uniprot.org/core/author"Persechino S."xsd:string
http://purl.uniprot.org/citations/22702340http://purl.uniprot.org/core/author"De Vito C."xsd:string
http://purl.uniprot.org/citations/22702340http://purl.uniprot.org/core/author"Calvanese A."xsd:string
http://purl.uniprot.org/citations/22702340http://purl.uniprot.org/core/author"Nesca A."xsd:string
http://purl.uniprot.org/citations/22702340http://purl.uniprot.org/core/author"Prinzi N."xsd:string
http://purl.uniprot.org/citations/22702340http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22702340http://purl.uniprot.org/core/name"Clin Endocrinol (Oxf)"xsd:string
http://purl.uniprot.org/citations/22702340http://purl.uniprot.org/core/pages"780-786"xsd:string
http://purl.uniprot.org/citations/22702340http://purl.uniprot.org/core/title"In papillary thyroid carcinoma BRAFV600E is associated with increased expression of the urokinase plasminogen activator and its cognate receptor, but not with disease-free interval."xsd:string
http://purl.uniprot.org/citations/22702340http://purl.uniprot.org/core/volume"77"xsd:string
http://purl.uniprot.org/citations/22702340http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/22702340
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