title: Use of BRAF v600e immunocytochemistry on FNA direct smears of papillary thyroid carcinoma.
abstract: BACKGROUND
  Mutations of v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) are identified in almost half of all papillary thyroid carcinomas (PTCs). These mutations are specific for PTC and may confer a worse prognosis. An immunohistochemical (IHC) stain for BRAF is commercially available and has been validated in surgical specimens. Fine-needle aspiration (FNA) is frequently used as a diagnostic tool for risk stratification of thyroid nodules. Therefore, the authors evaluated the performance of immunostaining with the anti-BRAF antibody VE1 on FNA direct smears.
  
  
  METHODS
  The authors identified 51 FNA specimens that had subsequent surgical resection specimens with a diagnosis of PTC. BRAF VE1 IHC was performed on the surgical specimens to determine their mutation status. The corresponding direct smears were then stained using the same VE1 stain to assess correlation.
  
  
  RESULTS
  Twenty-two of the 46 included surgical specimens were positive for BRAF mutations (47.8%) by IHC, consistent with the published rates. The paired cytologic smears from these cases revealed 65.3% concordance. The overall sensitivity of BRAF staining on cytologic smears was 63.6%, and the specificity was 58.3%. Concordance rates were highest in specimens that were diagnosed as malignant or suspicious for malignancy (75% and 85.7%, respectively). The negative predictive value increased to 77.8% when suspicious for follicular neoplasm/suspicious cases were combined.
  
  
  CONCLUSIONS
  Specimens that were malignant or suspicious on FNA were most likely to be BRAF concordant. Limitations to the interpretation of smears included low cellularity and obscuring blood, macrophages, or colloid. With further refinement, it is possible that BRAF immunocytochemistry can be applied prospectively to thyroid FNAs for risk stratification and to reduce false-negative rates.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Wobker
authors.affiliation: Department of Surgery, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Lawrence T
authors.initials: LT
authors.lastname: Kim
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Trevor G
authors.initials: TG
authors.lastname: Hackman
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Leslie G
authors.initials: LG
authors.lastname: Dodd
mesh_terms: D000368:Aged; D044963:Biopsy, Fine-Needle; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D002291:Carcinoma, Papillary; D004252:DNA Mutational Analysis; D005260:Female; D006785:Hospitals, University; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012189:Retrospective Studies; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D013965:Thyroidectomy / Q000379:methods
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF protein; fine-needle aspiration; human; immunohistocytochemistry; papillary thyroid carcinoma; thyroid gland