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

Lidija Jovanovic, Brett Delahunt, Bryan McIver, Norman L. Eberhardt, Alokananda Bhattacharya, Rod Lea, Stefan K.G. Grebe

Research output: Contribution to journalArticle

13 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)524-533
Number of pages10
JournalPathology
Volume42
Issue number6
DOIs
StatePublished - Oct 2010

Keywords

  • Allelic imbalances
  • Loss of heterozygosity
  • Multifocal papillary thyroid carcinoma
  • Phenotypic diversity

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Jovanovic, L., Delahunt, B., McIver, B., Eberhardt, N. L., Bhattacharya, A., Lea, R., & Grebe, S. K. G. (2010). Distinct genetic changes characterise multifocality and diverse histological subtypes in papillary thyroid carcinoma. Pathology, 42(6), 524-533. https://doi.org/10.3109/00313025.2010.508780