title: Analysis of differential BRAF(V600E) mutational status in multifocal papillary thyroid carcinoma: evidence of independent clonal origin in distinct tumor foci.
abstract: BACKGROUND
  Papillary thyroid cancers often occur as multiple foci. Multifocal cancers have been considered to have a poor prognosis because they are thought to be the consequence of intrathyroidal spread of the papillary cancer. However, to the authors' knowledge there has been little investigation into whether multifocal thyroid papillary carcinomas arise from the intrathyroidal spread of a single carcinoma or from independent primary tumors. To answer this question, the BRAF(V600E) mutational status of individual tumor foci was examined. This approach was justified because in the Korean population a high proportion (65%) of papillary carcinomas harbor the BRAF mutation.
  
  
  METHODS
  DNA was isolated from paraffin-embedded tissue samples of multifocal papillary thyroid carcinoma and the BRAF exon 15 was amplified by the polymerase chain reaction (PCR). The PCR product was digested with restriction endonuclease TspRI to test for the presence of the BRAF(V600E) (T1799A) mutation.
  
  
  RESULTS
  In all, 140 cancers from 61 patients diagnosed with multifocal papillary carcinoma were examined. The BRAF mutation was found in all the individual cancers in 29 (47.5%) of the patients (all-positive group) and the mutation was absent in all the individual cancers in 8 (13.1%) patients (all-negative group). However, in 24 (39.3%) patients, some of the individual cancers contained the BRAF mutation, whereas others did not (mixed group).
  
  
  CONCLUSIONS
  At least 39.3% of the multifocal papillary cancers in the Korean population that were examined could be attributed to independently arising papillary cancers rather than to intrathyroidal spread of single cancers.
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea.
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Park
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Park
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Lee
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Choi
authors.forename: Gheeyoung
authors.initials: G
authors.lastname: Choe
authors.forename: Hak-Chul
authors.initials: HC
authors.lastname: Jang
authors.forename: Seong Hoe
authors.initials: SH
authors.lastname: Park
authors.forename: Do Joon
authors.initials: DJ
authors.lastname: Park
authors.forename: Bo Youn
authors.initials: BY
authors.lastname: Cho
mesh_terms: D000328:Adult; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009378:Neoplasms, Multiple Primary / Q000235:genetics*; D016133:Polymerase Chain Reaction; D048493:Proto-Oncogene Proteins B-raf; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf