title: Reflex BRAF testing in thyroid fine-needle aspiration biopsy with equivocal and positive interpretation: a prospective study.
abstract: BACKGROUND
  The BRAF V600E mutation has been reported in 50%-80% of papillary thyroid carcinoma (PTC) cases and is highly specific for PTC. Reflex BRAF testing may improve the diagnostic accuracy of thyroid fine-needle aspiration (FNA) tests having equivocal cytologic interpretations and provide prognostic information that helps guide management in patients with PTC.
  
  
  METHODS
  Cases with equivocal thyroid FNA readings (indeterminate and suspicious for PTC) or a positive diagnosis for PTC and concomitant BRAF mutation analysis were included in this prospective study. BRAF mutation analysis was performed by polymerase chain reaction combined with single-strand conformation polymorphism gel electrophoresis using lavage fluid obtained from needle rinsing. The results of histopathologic follow-up were correlated with the cytologic interpretations and BRAF status.
  
  
  RESULTS
  One hundred fifty-seven FNAs with equivocal or positive cytologic interpretations were eligible for the study. All but one (99.4%) FNAs were found to have sufficient DNA quality and quantity for the assay. Based on the follow-up diagnosis of nodules after surgical resection, the sensitivity for diagnosing PTC was 63.3% with cytology alone and 80.0% with the combination of cytology and BRAF testing, respectively. No false positives were noted with either cytology or BRAF mutation analysis. All PTCs with extrathyroidal extension and of tall-cell variant were postive for BRAF mutation.
  
  
  CONCLUSIONS
  BRAF V600E mutation analysis can be easily performed on cytologic preparation using lavage fluids obtained from needle rinsing. By combining morphologic evaluation and BRAF testing, there is a substantial improvement in the preoperative identification of PTC when compared with cytology alone. Patients with equivocal cytologic diagnosis and BRAF V600E mutation are candidates for total thyroidectomy ± central lymph node dissection.
authors.affiliation: Department of Pathology, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Adebowale J
authors.initials: AJ
authors.lastname: Adeniran
authors.forename: Constantine
authors.initials: C
authors.lastname: Theoharis
authors.forename: Pei
authors.initials: P
authors.lastname: Hui
authors.forename: Manju L
authors.initials: ML
authors.lastname: Prasad
authors.forename: Lynwood
authors.initials: L
authors.lastname: Hammers
authors.forename: Tobias
authors.initials: T
authors.lastname: Carling
authors.forename: Robert
authors.initials: R
authors.lastname: Udelsman
authors.forename: David C
authors.initials: DC
authors.lastname: Chhieng
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D044963:Biopsy, Fine-Needle; D002277:Carcinoma; D002291:Carcinoma, Papillary; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013961:Thyroid Gland / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf