Distinct genetic changes characterise multifocality and diverse histological subtypes in papillary thyroid carcinoma

Abstract

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 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.

Key words:

• Multifocal papillary thyroid carcinoma
• phenotypic diversity
• allelic imbalances
• loss of heterozygosity
• BRAF^V600E mutation

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.