title: Role of BRAF molecular analysis in the management of papillary thyroid carcinoma: analysis of cytological and histological samples.
abstract: BACKGROUND
  Although fine needle aspiration (FNA) is the standard diagnostic test for the characterization of a suspicious thyroid nodule, in some cases cytological evaluation is inconclusive. The aim of this study was to determine the role of BRAF mutation in aiding diagnosis and to verify whether archival cytological samples could be suitable for molecular analysis.
  
  
  METHODS
  Eighty-five patients with suspicious (Thy4) or follicular (Thy3) lesions on cytology were resubmitted to a second FNA for BRAF mutation analysis. Of these, 56 subsequently underwent surgery. The usefulness of archival samples for molecular analysis was also studied in a second cohort of 42 patients with a confirmed diagnosis of papillary thyroid carcinoma for whom both archived paraffin-embedded histological samples and cytological smears were available. A further 15 patients with paired fresh FNA and archived cytological and histological samples were recruited.
  
  
  RESULTS
  BRAF mutation was found in the fresh FNA samples from 10 of 56 patients who had surgery with previous inconclusive cytology (4/45, 9%, Thy3 and 6/11, 55%, Thy4). The BRAF test showed a specificity and positive predictive value of 100% (26/26 and 10/10, respectively), sensitivity of 33% (10/30) and negative predictive value of 57% (26/46). There was absolute concordance between the BRAF results obtained with 42 histological and cytological archived samples. BRAF analysis on 15 archived cytological samples showed absolute concordance with histology, whereas there was one false negative on the matched fresh FNA.
  
  
  CONCLUSIONS
  BRAF analysis is a highly specific test that can facilitate cytological diagnosis in some cases and can also be performed on archived cytological samples.
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Capelli
authors.affiliation: Endocrine Surgery Unit, Morgagni-Piernatoni Hospital, Forlì, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Marfisi
authors.affiliation: Pathology Unit, S. Maria delle Croci Hospital, Ravenna, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Puccetti
authors.affiliation: Pathology Unit, Morgagni-Piernatoni Hospital, Forlì, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Saragoni
authors.affiliation: Pathology Unit, Morgagni-Piernatoni Hospital, Forlì, Italy.
authors.forename: F
authors.initials: F
authors.lastname: De Paola
authors.affiliation: Endocrine Surgery Unit, Morgagni-Piernatoni Hospital, Forlì, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Zaccaroni
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Chiadini
authors.affiliation: Endocrinology Unit, Morgagni-Piernatoni Hospital, Forlì, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Gagliardi
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Ferretti
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: W
authors.initials: W
authors.lastname: Zoli
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Ulivi
mesh_terms: D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D002291:Carcinoma, Papillary; D003581:Cytodiagnosis / Q000379:methods; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012680:Sensitivity and Specificity; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; cytological samples; fine needle aspiration; mutation; papillary thyroid carcinoma; thyroid nodules