title: The BRAF(V600E) mutation in papillary thyroid microcarcinoma: does the mutation have an impact on clinical outcome?
abstract: BACKGROUND
  An activating mutation in the gene BRAF has been correlated with poorer prognosis and more aggressive clinical course in papillary thyroid carcinoma (PTC). We therefore hypothesized that the good prognosis, high 5-year disease-free rate and high survival rate of patients with less aggressive papillary thyroid microcarcinoma (pT1aNo-x) would be associated with a lower incidence of the BRAF(V600E) mutation.
  
  
  OBJECTIVE
  To evaluate the frequency of the activating mutation BRAF(V600E) in low-risk papillary thyroid microcarcinoma (pT1aNo-x at the moment of diagnosis) and the association of the mutation with the clinical outcome in a retrospective analysis.
  
  
  METHODS
  BRAF(V600E) was characterized in 113 PTC patients diagnosed with pT1aNo-x (one PTC focus with a diameter <1 cm, without lymph node or distant metastases according to IUCC/AJCC TNM staging system 2010). Genotyping was performed on DNA extracted from thyroid tumour tissue using direct capillary sequencing, and allele-specific amplification PCR was used to resolve equivocal results. Retrospective analysis of the clinical course of PTC was then correlated with BRAF status in the primary tumour tissue.
  
  
  RESULTS
  The BRAF(V600E) mutation was detected in 78 of the 113 pT1aNo-x patients (69·0%). We observed no persistence, locoregional recurrence, lymph node or distant metastases or deaths in the study group during the 12-year study (January 2001 to December 2012).
  
  
  CONCLUSIONS
  The presence of the activating BRAF(V) (600E) mutation in a significant percentage of papillary thyroid microcarcinoma indicates that further analyses are required to verify its usefulness as a predictor of clinical outcome in PTC. In this study, there was no correlation between BRAF-positive primary focus of papillary microcarcinoma and more aggressive or recurrent disease.
authors.affiliation: Department of Endocrinology and Nuclear Medicine, Holycross Cancer Centre, Kielce, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Walczyk
authors.forename: Aldona
authors.initials: A
authors.lastname: Kowalska
authors.forename: Artur
authors.initials: A
authors.lastname: Kowalik
authors.forename: Jacek
authors.initials: J
authors.lastname: Sygut
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Wypiórkiewicz
authors.forename: Renata
authors.initials: R
authors.lastname: Chodurska
authors.forename: Liliana
authors.initials: L
authors.lastname: Pięciak
authors.forename: Stanisław
authors.initials: S
authors.lastname: Góźdź
mesh_terms: D000368:Aged; D000483:Alleles; D002291:Carcinoma, Papillary / Q000235:genetics*; D003062:Codon; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015994:Incidence; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012189:Retrospective Studies; D013964:Thyroid Neoplasms / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D003062:Codon; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf