title: 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.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Genetic Bases of Thyroid Tumor Laboratory, Division of Genetics, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Gisele
authors.initials: G
authors.lastname: Oler
authors.forename: Janete M
authors.initials: JM
authors.lastname: Cerutti
mesh_terms: D001938:Brazil; D002291:Carcinoma, Papillary / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007454:Iodides / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D027981:Symporters / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics*; D000099209:Sodium-Iodide Symporters
chemical_list: D007454:Iodides; D048493:Proto-Oncogene Proteins B-raf; D027981:Symporters; D000099209:Sodium-Iodide Symporters; C482119:BRAF protein, human