title: The BRAF mutation is useful for prediction of clinical recurrence in low-risk patients with conventional papillary thyroid carcinoma.
abstract: BACKGROUND
  The activating BRAF(V600E) mutation is the most common genetic alteration reported in papillary thyroid carcinoma (PTC). While some reports suggest the BRAF(V600E) mutation is associated with factors predicting a poor prognosis and recurrence, this remains a controversial issue.
  
  
  OBJECTIVE
  To determine whether the presence of the BRAF(V600E) mutation is a prognostic indicator for clinical recurrence in low-risk patients with conventional PTC.
  
  
  METHODS
  The study involved 203 conventional PTC patients who underwent total or near-total thyroidectomy followed by immediate 131I ablation of the remnants. Patients with antithyroglobulin antibodies and those with extracervical metastases at presentation were excluded. DNA was extracted from paraffin-embedded tumour specimens, and the presence of the BRAF(V600E) mutation was evaluated using PCR amplification and direct sequencing.
  
  
  RESULTS
  The BRAF(V600E) mutation was found to be present in 149 (73.4%) of 203 patients. The BRAF(V600E) mutation was correlated with male gender (P = 0.006) and with tumour size (P = 0.005). While there appeared to be an association between the BRAF(V600E) mutation and extrathyroid extension, this did not reach statistical significance (P = 0.062). During follow-up of the 203 patients (median 7.3 years; range 0.7-10.0 years), 36 (18%) patients experienced recurrence. While univariate analysis showed the BRAF(V600E) mutation was associated with tumour recurrence (21% with mutation vs 7% without mutation; P = 0.037), this association was not shown following multivariate analyses adjusting for the clinicopathological prognostic factors of age, gender, tumour size, extrathyroid extension, multifocality and lymph node metastasis.
  
  
  CONCLUSIONS
  Although the BRAF(V600E) mutation was found to be associated with a higher clinical recurrence of disease in low-risk conventional PTC patients, it was not an independent predictor.
authors.affiliation: Department of Internal Medicine, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Tae Yong
authors.initials: TY
authors.lastname: Kim
authors.forename: Won Bae
authors.initials: WB
authors.lastname: Kim
authors.forename: Yoon Soo
authors.initials: YS
authors.lastname: Rhee
authors.forename: Ja Young
authors.initials: JY
authors.lastname: Song
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Gyungyub
authors.initials: G
authors.lastname: Gong
authors.forename: Seungkoo
authors.initials: S
authors.lastname: Lee
authors.forename: Sang Yoon
authors.initials: SY
authors.lastname: Kim
authors.forename: Seong Chul
authors.initials: SC
authors.lastname: Kim
authors.forename: Suck Joon
authors.initials: SJ
authors.lastname: Hong
authors.forename: Young Kee
authors.initials: YK
authors.lastname: Shong
mesh_terms: D000328:Adult; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D005260:Female; D019788:Fluorodeoxyglucose F18; D005500:Follow-Up Studies; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality; D017354:Point Mutation; D049268:Positron-Emission Tomography; D011379:Prognosis; D016016:Proportional Hazards Models; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D016019:Survival Analysis; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D013965:Thyroidectomy
chemical_list: D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf