title: Diagnostic value of immunohistochemistry for the detection of the BRAF(V600E) mutation in papillary thyroid carcinoma: comparative analysis with three DNA-based assays.
abstract: BACKGROUND
  The aim of this study was to compare the detection of BRAF(V600E) by immunohistochemistry (IHC) using a mutation-specific antibody with molecular biology methods for evaluation of papillary thyroid carcinoma (PTC) patients.
  
  
  METHODS
  This study concerned 198 consecutive conventional PTC patients, of which the majority were women (133/198; 67%), with a mean age of 56 years (range 19-79 years). BRAF mutation analysis was performed using DNA-based (direct sequencing, pyrosequencing, and SNaPshot) and IHC (VE1 antibody) methods. The sensitivity and specificity of IHC for BRAF(V600E) was compared with the molecular biology data.
  
  
  RESULTS
  A BRAF mutational result was obtained in 194 cases. A BRAF(V600E) mutation was detected in 153/194 (79%) cases of PTC when using at least one molecular method, and in 151/194 (78%) cases with IHC. No false positive results were noted using IHC to detect the BRAF(V600E) mutation. Besides this mutation, other rare BRAF mutations (BRAF(V600K) and BRAF(K601E)), used as negative controls, were consistently negative with IHC. The sensitivity and specificity of IHC for the detection of this mutation were 98.7% and 100% respectively. The IHC test demonstrated excellent performance at a level equivalent to two DNA-based counterparts (pyrosequencing and SNaPshot). Failure to achieve a result was more frequent with the direct sequencing method than with the three other methods.
  
  
  CONCLUSIONS
  IHC using the VE1 antibody is a specific and sensitive method for the detection of the BRAF(V600E) mutation in PTC. IHC may be an alternative to molecular biology approaches for the routine detection of this mutation in PTC patients.
authors.affiliation: 1 Team 3, Faculty of Medicine, French Institute of Health and Medical Research (INSERM) U1081, French National Center for Scientific Research (CNRS) UMR 7284, Institute for Research on Cancer and Aging, Nice, France .
authors.forename: Marius I
authors.initials: MI
authors.lastname: Ilie
authors.forename: Sandra
authors.initials: S
authors.lastname: Lassalle
authors.forename: Elodie
authors.initials: E
authors.lastname: Long-Mira
authors.forename: Christelle
authors.initials: C
authors.lastname: Bonnetaud
authors.forename: Olivier
authors.initials: O
authors.lastname: Bordone
authors.forename: Virginie
authors.initials: V
authors.lastname: Lespinet
authors.forename: Aude
authors.initials: A
authors.lastname: Lamy
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Sabourin
authors.forename: Juliette
authors.initials: J
authors.lastname: Haudebourg
authors.forename: Catherine
authors.initials: C
authors.lastname: Butori
authors.forename: Nicolas
authors.initials: N
authors.lastname: Guevara
authors.forename: Isabelle
authors.initials: I
authors.lastname: Peyrottes
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Sadoul
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bozec
authors.forename: José
authors.initials: J
authors.lastname: Santini
authors.forename: David
authors.initials: D
authors.lastname: Capper
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Emile
authors.forename: Véronique
authors.initials: V
authors.lastname: Hofman
authors.forename: Paul
authors.initials: P
authors.lastname: Hofman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D000918:Antibody Specificity; D062005:Biopsy, Large-Core Needle; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002291:Carcinoma, Papillary; D004273:DNA, Neoplasm / Q000737:chemistry / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism*; D009367:Neoplasm Staging; D048493:Proto-Oncogene Proteins B-raf / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012680:Sensitivity and Specificity; D000077273:Thyroid Cancer, Papillary; D013961:Thyroid Gland / Q000378:metabolism* / Q000473:pathology; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D004273:DNA, Neoplasm; D050505:Mutant Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf