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High prevalence of BRAF mutation in a Brazilian cohort of patients with sporadic papillary thyroid carcinomas†
Correlation with more aggressive phenotype and decreased expression of iodide-metabolizing genes
Article first published online: 17 JAN 2009
Copyright © 2009 American Cancer Society
Volume 115, Issue 5, pages 972–980, 1 March 2009
How to Cite
Oler, G. and Cerutti, J. M. (2009), High prevalence of BRAF mutation in a Brazilian cohort of patients with sporadic papillary thyroid carcinomas. Cancer, 115: 972–980. doi: 10.1002/cncr.24118
Dr. Oler is a scholar from São Paulo State Research Support Foundation (FAPESP) and Dr. Cerutti is an investigator of the Brazilian Research Council (CNPq).
- Issue published online: 18 FEB 2009
- Article first published online: 17 JAN 2009
- Manuscript Accepted: 22 SEP 2008
- Manuscript Revised: 26 AUG 2008
- Manuscript Received: 19 JUN 2008
- São Paulo State Research Foundation (FAPESP). Grant Number: 05/60330-8
- papillary thyroid carcinoma;
- clinicopathologic features;
- NIS, TSHR
Although several studies undoubtedly demonstrated that BRAF mutation is an important genetic event in the pathogenesis of papillary thyroid carcinoma (PTC), its prognostic significance and correlation with less differentiated states remains unclear. It has been suggested that the discrepancy may be at least partially due to the insufficient number of cases analyzed, epidemiologic factors, and a combination of different variants of PTC included in these studies.
In this context, the prevalence of the BRAF mutation in a Brazilian cohort of PTCs (n = 120) was first assessed and correlated with clinicopathologic features. The BRAF exon 15 mutation was evaluated by direct sequencing. Furthermore, using quantitative polymerase chain reaction, the issue of whether the expression level of the iodide-metabolizing genes (NIS and TSHR) was correlated with BRAF mutational status was investigated.
A high prevalence of the BRAF mutation was found in PTC cases (48%). The BRAF mutation was found to be significantly associated with the classic variant of PTC (66%; P < .0001), although it was found in the follicular variant as well (21%). Subtype stratification demonstrated that the BRAF V600E mutation was associated with tumor size, extrathyroid invasion, the presence of lymph node metastasis and risk of disease recurrence, and mortality in patients with the classic variant of PTC. Moreover, the expression levels of NIS and TSHR were remarkably lower in PTCs harboring the BRAF V600E mutation.
These findings provide further evidence that BRAF might be associated with a more aggressive phenotype and less differentiated state due to decreased expression of iodide-metabolizing genes. The search for a BRAF mutation in the current study population appears to be valuable for predicting prognosis and guiding management in patients with PTC. Cancer 2009. © 2009 American Cancer Society.