title: BRAF mutation in follicular variant of papillary thyroid carcinoma is associated with unfavourable clinicopathological characteristics and malignant features on ultrasonography.
abstract: OBJECTIVE
  Follicular variant of papillary thyroid carcinoma (FVPTC) is a common variant of papillary thyroid carcinoma (PTC), but the association between BRAF mutation and the clinicopathological and ultrasonographical characteristics of FVPTC has not been well studied. The aim of this study was to determine the significance of BRAF mutation in FVPTC.
  
  
  METHODS
  The medical records of the 137 patients with >5 mm FVPTCs and known BRAF mutation status in the interested nodule were reviewed. BRAF mutation analysis was performed routinely and prospectively by Sanger sequencing. Clinicopathological and ultrasonographical characteristics were compared between BRAF mutation-positive and BRAF mutation-negative groups.
  
  
  RESULTS
  BRAF mutation was detected in 35 (25·5%) patients. The BRAF mutation-positive group was associated with smaller tumour size (P = 0·022), extrathyroidal extension (P = 0·001), multifocality (P = 0·046) and higher (III/IV) TNM stages (P = 0·005). In multivariable analysis, higher (III/IV) TNM stage was an independent predictive factor for BRAF mutation-positive status (adjusted OR 2·966, 95% CI 1·321-6·663). In diagnosis of FVPTC, the presence of BRAF mutation was associated with malignant features on ultrasonography (P < 0·001) and higher incidence of suspicious for malignancy or malignant diagnosis on the fine needle aspiration cytology (P = 0·023). Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of US for detecting BRAF mutation were 82·9%, 57·8%, 40·3%, 90·8% and 64·2%, respectively. Conclusions BRAF mutation in FVPTC is associated with unfavourable clinicopathological characteristics and malignant features on ultrasonography and may be a potential prognostic factor as it is in classical PTC.
authors.affiliation: Department of Surgery, Seoul National University Hospital and College of Medicine, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Young Jun
authors.initials: YJ
authors.lastname: Chai
authors.forename: Su-jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Soo Chin
authors.initials: SC
authors.lastname: Kim
authors.forename: Do Hoon
authors.initials: do H
authors.lastname: Koo
authors.forename: Hye Sook
authors.initials: HS
authors.lastname: Min
authors.forename: Kyu Eun
authors.initials: KE
authors.lastname: Lee
authors.forename: Ji-hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Yeo-Kyu
authors.initials: YK
authors.lastname: Youn
mesh_terms: D000328:Adult; D002277:Carcinoma / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D002291:Carcinoma, Papillary; D018265:Carcinoma, Papillary, Follicular / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D014463:Ultrasonography
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf