title: Analysis of immunocytochemical and molecular BRAF expression in thyroid carcinomas: a cytohistologic institutional experience.
abstract: BACKGROUND
  It has been generally demonstrated that the valine-to-glutamic acid substitution at position 600 (V600E) in the v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) gene is an effective diagnostic/prognostic marker mainly for papillary thyroid carcinoma (PTC). The detection of this mutation typically has been achieved using DNA-based techniques. The recently introduced monoclonal V600E antibody (clone VE1) is likely to be an alternative strategy for detecting this mutation in thyroid lesions. The authors investigated molecular and immunocytohistochemical BRAF analyses in a prospective series of samples from patients with PTC.
  
  
  METHODS
  Fifty-five prospective cytohistologic samples that were diagnosed as PTC were studied using both DNA BRAF testing and the VE1 antibody. The intensity of VE1 expression was graded from 0 (negative) to 3+ (strong).
  
  
  RESULTS
  All diagnoses were histologically confirmed. In total, 37 samples with mutated BRAF and 18 samples with wild-type BRAF were reported with 100% cytohistologic concordance. Cytologic VE1 expression revealed 25 negative samples (including 16 with 0 expression and 9 with 1+ expression) and 30 positive samples (including 16 with 2+ expression and 14 with 3+ expression). On histology, there were 27 negative samples (20 with 0 expression and 7 with 1+ expression) and 28 positive samples (14 with 2+ expression and 14 with 3+ expression). Four specimens with the BRAF mutation had discrepancies in VE1 intensity between cytology and histology. Furthermore, 6 BRAF-mutated samples produced negative VE1 results.
  
  
  CONCLUSIONS
  Although it has limitations, the VE1 antibody represents a feasible first-line approach for evaluating BRAF mutation status and may be a valid tool in the selection of samples for molecular analysis. The current report highlights the statistically significant difference between molecular and VE1 positivity in PTC (P < .0001). Nevertheless, in the authors' experience, BRAF mutations are more accurate for identifying VE1-negative cases.
authors.affiliation: Division of Anatomic Pathology and Histology, "Agostino Gemelli" School of Medicine, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Esther Diana
authors.initials: ED
authors.lastname: Rossi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Martini
authors.forename: Sara
authors.initials: S
authors.lastname: Capodimonti
authors.forename: Tonia
authors.initials: T
authors.lastname: Cenci
authors.forename: Patrizia
authors.initials: P
authors.lastname: Straccia
authors.forename: Basilio
authors.initials: B
authors.lastname: Angrisani
authors.forename: Costantino
authors.initials: C
authors.lastname: Ricci
authors.forename: Paola
authors.initials: P
authors.lastname: Lanza
authors.forename: Celestino Pio
authors.initials: CP
authors.lastname: Lombardi
authors.forename: Alfredo
authors.initials: A
authors.lastname: Pontecorvi
authors.forename: Luigi Maria
authors.initials: LM
authors.lastname: Larocca
authors.forename: Guido
authors.initials: G
authors.lastname: Fadda
mesh_terms: D000328:Adult; D000368:Aged; D001707:Biopsy, Needle; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF mutation; VE1 immunomarker; immunochemistry; liquid-based cytology; thyroid papillary carcinoma