title: Detection of BRAFV600E mutation on fine needle aspiration specimens of thyroid nodule refines cyto-pathology diagnosis, especially in BRAF600E mutation-prevalent area.
abstract: BACKGROUND
  Between 10 and 30% of the fine needle aspiration biopsies (FNABs) of thyroid nodules are diagnosed as 'indeterminate'. A molecular diagnostic method is needed to reduce unnecessary surgery in this group. In Korea, most thyroid cancer is the classic papillary type and the BRAF(V600E) mutation is highly prevalent.
  
  
  OBJECTIVE
  To evaluate the role of pre-operative detection of BRAF(V600E) mutation in the FNAB specimens of thyroid nodules in a BRAF(V600E) mutation-prevalent geographical area.
  
  
  METHODS
  In 137 specimens of FNAB (107 papillary thyroid carcinomas (PTC); 3 follicular thyroid carcinomas (FTC); 2 undifferentiated thyroid carcinomas; 25 benign lesions), both direct DNA sequencing and PCR-RFLP were used for detecting the BRAF(V600E) mutation. The sensitivity and specificity were calculated. We analysed the association between BRAF(V600E) mutation and the clinico-pathological parameters.
  
  
  RESULTS
  The BRAF(V600E) mutation was present in 93 (83%) of 112 thyroid cancers. Direct DNA sequencing showed a sensitivity of 83.0% and a specificity of 96.0%. The sensitivity and specificity of PCR-RFLP were 78.6% and 80.0%, respectively. Among 25 cases with indeterminate FNAB cytology, 8 patients had malignant lesions (5 PTC and 3 FTC). Three (60%) of 5 PTCs and 1 out of 17 benign lesions had BRAF(V600E) mutation (only one false positive case and the definitive pathology showed atypical nodular hyperplasia that could be a premalignant lesion). The diagnostic accuracy of this molecular method in only the 25 indeterminate nodules was 76% (19/25). No mutation was found in 3 FTCs. Among 107 PTCs, there was no significant association of the BRAF(V600E) mutation with the known risk factors.
  
  
  CONCLUSIONS
  Detection of the BRAF(V600E) mutation in FNAB specimens refines the FNAB-cytology diagnosis, especially in a BRAF(V600E) mutation-prevalent area. Direct DNA sequencing was a more reliable method than PCR-RFLP for detecting the BRAF(V600E) mutation with a high sensitivity and specificity.
authors.affiliation: Research Institute and Hospital, National Cancer Centre, Goyang, Gyeonggi, Korea.
authors.forename: Ki-wook
authors.initials: KW
authors.lastname: Chung
authors.forename: Sun Kyung
authors.initials: SK
authors.lastname: Yang
authors.forename: Geon Kook
authors.initials: GK
authors.lastname: Lee
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Kim
authors.forename: Soim
authors.initials: S
authors.lastname: Kwon
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: Lee
authors.forename: Do Joon
authors.initials: DJ
authors.lastname: Park
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Lee
authors.forename: Bo Youn
authors.initials: BY
authors.lastname: Cho
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Lee
authors.forename: Sun Wook
authors.initials: SW
authors.lastname: Kim
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics; D000328:Adult; D000368:Aged; D044963:Biopsy, Fine-Needle; D002291:Carcinoma, Papillary / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D018265:Carcinoma, Papillary, Follicular / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012680:Sensitivity and Specificity; D013964:Thyroid Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D016606:Thyroid Nodule / Q000208:ethnology / Q000235:genetics* / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf