In papillary thyroid carcinoma BRAFV600Eis associated with increased expression of the urokinase plasminogen activator and its cognate receptor, but not with disease-free interval

Autor: Severino Persechino, Enrico De Antoni, Palermo S, Salvatore Ulisse, Maria Rosa Pelizzo, Antonio Catania, Enke Baldini, Salvatore Sorrenti, Corrado De Vito, Susi Barollo, Natalie Prinzi, Caterina Mian, A. Calvanese, Lucio Gnessi, Massimino D'Armiento, Angela Nesca
Rok vydání: 2012
Předmět:
Male
endocrine system diseases
Endocrinology
Diabetes and Metabolism
medicine.medical_treatment
Polymerase Chain Reaction
Papillary thyroid cancer
Endocrinology
upa
Child
skin and connective tissue diseases
Lymph node
Aged
80 and over
Middle Aged
medicine.anatomical_structure
Thyroid Cancer
Papillary
Female
upar
braf
ptc
prognosis
medicine.drug
Adult
Proto-Oncogene Proteins B-raf
medicine.medical_specialty
Adolescent
Context (language use)
Biology
Cell Line
Receptors
Urokinase Plasminogen Activator
Thyroid carcinoma
Young Adult
Internal medicine
medicine
Animals
Humans
Thyroid Neoplasms
neoplasms
Aged
Urokinase
Carcinoma
Thyroidectomy
medicine.disease
Urokinase-Type Plasminogen Activator
Carcinoma
Papillary
digestive system diseases
Rats
Urokinase receptor
enzymes and coenzymes (carbohydrates)
V600E
Zdroj: Clinical Endocrinology. 77:780-786
ISSN: 0300-0664
DOI: 10.1111/j.1365-2265.2012.04465.x
Popis: 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.
Databáze: OpenAIRE
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