TY - JOUR
T1 - Distinct genetic changes characterise multifocality and diverse histological subtypes in papillary thyroid carcinoma
AU - Jovanovic, Lidija
AU - Delahunt, Brett
AU - McIver, Bryan
AU - Eberhardt, Norman L.
AU - Bhattacharya, Alokananda
AU - Lea, Rod
AU - Grebe, Stefan K.G.
N1 - Funding Information:
Acknowledgements: Supported by a grant from the Cancer Society of New Zealand, the Wellington Medical Research Foundation, NIH grant CA80117, and funds from the Wellington School of Medicine and Health Sciences, the Mayo Clinic, and the Price Foundation.
PY - 2010/10
Y1 - 2010/10
N2 - Aims: 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 BRAFV600E 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 BRAFV600E 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.
AB - Aims: 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 BRAFV600E 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 BRAFV600E 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.
KW - Allelic imbalances
KW - Loss of heterozygosity
KW - Multifocal papillary thyroid carcinoma
KW - Phenotypic diversity
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U2 - 10.3109/00313025.2010.508780
DO - 10.3109/00313025.2010.508780
M3 - Article
C2 - 20854070
AN - SCOPUS:77956921006
SN - 0031-3025
VL - 42
SP - 524
EP - 533
JO - Pathology
JF - Pathology
IS - 6
ER -