title: BRAFV600Emutation as a predictor of thyroid malignancy in indeterminate nodules: A systematic review and meta-analysis.
abstract: BACKGROUND
  Thyroid nodules are usually diagnosed using fine-needle aspiration (FNA). The sensitivity limitations of FNA result in 10-30% of nodules being classified as "indeterminate". The BRAFV600Emutation is associated with papillary thyroid carcinoma (PTC). We conducted a systemic review and meta-analysis to evaluate the diagnostic utility of the BRAFV600Emutation in indeterminate nodules.
  
  
  METHODS
  PUBMED and EMBASE were searched for studies testing for the BRAFV600Einvolving indeterminate nodules (Thy3a, Thy3f, Thy4) and containing information on final surgical histopathology. Thirty two studies involving 3150 indeterminate nodules were included in the analysis.
  
  
  RESULTS
  The overall sensitivity and specificity for BRAFV600Efor the diagnosis of thyroid malignancy was 0.40 (95% CI: 0.32-0.48) and 1.00 (95% CI: 0.98-1.00) respectively. The diagnostic odds ratio (DOR) was 205.4 (95% CI: 40.1-1052). With a Fagan plot, the post-test probability of thyroid cancer, given a negative mutation was 6%, but this rose to 92% with a positive result. On subgroup analysis, for Thy3a nodules, the pooled sensitivity and specificity for thyroid malignancy was 0.21 (95% CI: 0.13-0.34) and 1.00 (95% CI: 0.98-1.00). For Thy3f nodules, the pooled sensitivity and specificity was 0.09 (95% CI: 0.03-0.20) and 1.00 (95% CI: 0.05-1.00) respectively. For Thy4 nodules, the corresponding sensitivity and specificity was 0.58 (95% CI: 0.5-0.64) and 0.99 (95% CI: 0.95-1.00) respectively.
  
  
  CONCLUSIONS
  Despite a high specificity for thyroid cancer, BRAFV600Emutation has a low overall sensitivity and therefore has a limited diagnostic value as a single screening test.
authors.affiliation: Department of Academic Surgery, National University of Ireland (Cork), Cork University Hospital (CUH), Wilton, Cork, Ireland. Electronic address: marceljinih@rcsi.ie.
authors.forename: M
authors.initials: M
authors.lastname: Jinih
authors.affiliation: Department of Academic Surgery, National University of Ireland (Cork), Cork University Hospital (CUH), Wilton, Cork, Ireland.
authors.forename: N
authors.initials: N
authors.lastname: Foley
authors.affiliation: Department of Academic Surgery, National University of Ireland (Cork), Cork University Hospital (CUH), Wilton, Cork, Ireland.
authors.forename: O
authors.initials: O
authors.lastname: Osho
authors.affiliation: Department of Academic Surgery, National University of Ireland (Cork), Cork University Hospital (CUH), Wilton, Cork, Ireland.
authors.forename: L
authors.initials: L
authors.lastname: Houlihan
authors.affiliation: Department of Academic Surgery, National University of Ireland (Cork), Cork University Hospital (CUH), Wilton, Cork, Ireland.
authors.forename: A A
authors.initials: AA
authors.lastname: Toor
authors.affiliation: Department of Academic Surgery, National University of Ireland (Cork), Cork University Hospital (CUH), Wilton, Cork, Ireland.
authors.forename: J Z
authors.initials: JZ
authors.lastname: Khan
authors.affiliation: Department of Academic Surgery, National University of Ireland (Cork), Cork University Hospital (CUH), Wilton, Cork, Ireland.
authors.forename: A A
authors.initials: AA
authors.lastname: Achakzai
authors.affiliation: Department of Academic Surgery, National University of Ireland (Cork), Cork University Hospital (CUH), Wilton, Cork, Ireland.
authors.forename: H P
authors.initials: HP
authors.lastname: Redmond
mesh_terms: D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis*; D006801:Humans; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012680:Sensitivity and Specificity; D016606:Thyroid Nodule / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF V600E mutation; Indeterminate thyroid nodule; Thy3a; Thy3f; Thy4