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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.
Clin Endocrinol (Oxf). 2012 Nov; 77(5):780-6.CE

Abstract

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.

Authors+Show Affiliations

Department of Experimental Medicine, University of Rome, Rome, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22702340

Citation

Ulisse, Salvatore, et al. "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." Clinical Endocrinology, vol. 77, no. 5, 2012, pp. 780-6.
Ulisse S, Baldini E, Sorrenti S, et al. 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. Clin Endocrinol (Oxf). 2012;77(5):780-6.
Ulisse, S., Baldini, E., Sorrenti, S., Barollo, S., Prinzi, N., Catania, A., Nesca, A., Gnessi, L., Pelizzo, M. R., Mian, C., De Vito, C., Calvanese, A., Palermo, S., Persechino, S., De Antoni, E., & D'Armiento, M. (2012). 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. Clinical Endocrinology, 77(5), 780-6. https://doi.org/10.1111/j.1365-2265.2012.04465.x
Ulisse S, et al. 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. Clin Endocrinol (Oxf). 2012;77(5):780-6. PubMed PMID: 22702340.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Ulisse,Salvatore, AU - Baldini,Enke, AU - Sorrenti,Salvatore, AU - Barollo,Susi, AU - Prinzi,Natalie, AU - Catania,Antonio, AU - Nesca,Angela, AU - Gnessi,Lucio, AU - Pelizzo,Maria R, AU - Mian,Caterina, AU - De Vito,Corrado, AU - Calvanese,Anna, AU - Palermo,Silvio, AU - Persechino,Severino, AU - De Antoni,Enrico, AU - D'Armiento,Massimino, PY - 2012/6/19/entrez PY - 2012/6/19/pubmed PY - 2013/3/13/medline SP - 780 EP - 6 JF - Clinical endocrinology JO - Clin. Endocrinol. (Oxf) VL - 77 IS - 5 N2 - 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. SN - 1365-2265 UR - https://www.unboundmedicine.com/medline/citation/22702340/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_ L2 - https://doi.org/10.1111/j.1365-2265.2012.04465.x DB - PRIME DP - Unbound Medicine ER -