Thyroid gland clonality revisited: The embryonal patch size of the normal human thyroid gland is very large, suggesting X-chromosome inactivation tumor clonality studies of thyroid tumors have to be interpreted with caution

Lidija Jovanovic, Brett Delahunt, Bryan McIver, Norman L. Eberhardt, Stefan K.G. Grebe

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

It is widely assumed thyroid carcinomas, adenomas, and many hyperplastic nodules are monoclonal. This belief is based on X-chromosome inactivation analyses of thyroid tumors. However, X-chromosome inactivation studies of tumors are informative only when interpreted in the context of the clonal composition of the surrounding normal tissue, and in the case of thyroid tissue, such analyses have never been systematically performed in humans. The aim of this study was to determine the embryonal patch size of the human thyroid gland. We performed human androgen receptor (HUMARA) assay-based X-chromosome inactivation analysis on 20 micro-dissected normal thyroid specimens from 16 female subjects. Monoclonality was observed in 70% of tested specimens, and polyclonal X-inactivation patterns were present in only 30% of specimens. According to our results the monoclonal patch size of normal human thyroid tissue is between 48 mm2 and 128 mm2 (1-4 × 105 thyrocytes). Our data indicate that normal thyroid epithelium is organized into large stem cell-derived monoclonal patches. Therefore, monoclonality in neoplastic and hyperplastic lesions may just be a reflection of normal thyroid epithelium clonal composition.

Original languageEnglish (US)
Pages (from-to)3284-3291
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume88
Issue number7
DOIs
StatePublished - Jul 1 2003

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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