Distinct genetic changes characterise multifocality and diverse histological subtypes in papillary thyroid carcinoma.
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.
Jovanovic
Lidija
L
Department of Pathology and Molecular Medicine, Wellington School of Medicine and Health Sciences, University of Otago, Wellington, New Zealand.
Delahunt
Brett
B
McIver
Bryan
B
Eberhardt
Norman L
NL
Bhattacharya
Alokananda
A
Lea
Rod
R
Grebe
Stefan K G
SK
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
D014408:Biomarkers, Tumor; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf