title: Distinct genetic changes characterise multifocality and diverse histological subtypes in papillary thyroid carcinoma.
abstract: OBJECTIVE
  This study was undertaken to investigate the genetic factors underlying the development of multifocality and phenotypic diversity in multifocal papillary thyroid carcinoma (mPTC).
  
  
  METHODS
  Loss of heterozygosity (LOH) and BRAF(V600E) mutation status were analysed in a total of 55 individual tumour foci from 18 cases of mPTC. The genetic findings and morphology of tumour foci were then compared.
  
  
  RESULTS
  Multifocal PTC LOH rates were higher than observed previously in solitary PTC. Different patterns of LOH and BRAF(V600E) positivity separated follicular variant tumours and tumour foci from other PTC histological subtypes. In five cases, genetic alterations were detected in morphologically normal thyroid epithelium.
  
  
  CONCLUSIONS
  These findings support the concept that multifocal PTCs develop through clonal selection from a field of pre-neoplastic cells, with morphotype differentiation correlating with specific tumour-genetic alterations. The relatively high genetic disarray in multifocal PTC may underlie their ability to spread throughout the thyroid gland.
authors.affiliation: Department of Pathology and Molecular Medicine, Wellington School of Medicine and Health Sciences, University of Otago, Wellington, New Zealand.
authors.forename: Lidija
authors.initials: L
authors.lastname: Jovanovic
authors.forename: Brett
authors.initials: B
authors.lastname: Delahunt
authors.forename: Bryan
authors.initials: B
authors.lastname: McIver
authors.forename: Norman L
authors.initials: NL
authors.lastname: Eberhardt
authors.forename: Alokananda
authors.initials: A
authors.lastname: Bhattacharya
authors.forename: Rod
authors.initials: R
authors.lastname: Lea
authors.forename: Stefan K G
authors.initials: SK
authors.lastname: Grebe
mesh_terms: D000231:Adenocarcinoma, Papillary / Q000235:genetics* / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002648:Child; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf