This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jovanovic, L. Articles by Grebe, S. K. G. Search for Related Content PubMed PubMed Citation Articles by Jovanovic, L. Articles by Grebe, S. K. G.

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

Department of Pathology and Molecular Medicine (L.J., B.D.), Wellington School of Medicine and Health Sciences, Wellington 6002, New Zealand; Departments of Medicine (B.M., N.L.E., S.K.G.G.), Biochemistry and Molecular Biology (N.L.E.), and Laboratory Medicine and Pathology (S.K.G.G.), Mayo Foundation and Clinic, Rochester, Minnesota 55905

Address all correspondence and requests for reprints to: Stefan K. G. Grebe, M.D., Endocrine Lab, Hilton 730, Department of Laboratory Medicine and Pathology, Mayo Foundation and Clinic, 200 First Street SW, Rochester, Minnesota 55905 E-mail: grebe.stefan{at}mayo.edu.

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 microdissected 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 x 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.

This work was supported by a grant from the Cancer Society of New Zealand (to S.K.G.G.), NIH Grant CA80117 (to N.L.E.), and funds from the Wellington School of Medicine and Health Sciences and the Mayo Foundation and Clinic.

Abbreviation: HUMARA, Human androgen receptor gene.

This article has been cited by other articles:

				R. P. McCarthy, M. Wang, T. D. Jones, R. W. Strate, and L. Cheng Molecular Evidence for the Same Clonal Origin of Multifocal Papillary Thyroid Carcinomas Clin. Cancer Res., April 15, 2006; 12(8): 2414 - 2418. [Abstract] [Full Text] [PDF]

				T. M. Shattuck, W. H. Westra, P. W. Ladenson, and A. Arnold Independent Clonal Origins of Distinct Tumor Foci in Multifocal Papillary Thyroid Carcinoma N. Engl. J. Med., June 9, 2005; 352(23): 2406 - 2412. [Abstract] [Full Text] [PDF]

				K. Krohn, D. Fuhrer, Y. Bayer, M. Eszlinger, V. Brauer, S. Neumann, and R. Paschke Molecular Pathogenesis of Euthyroid and Toxic Multinodular Goiter Endocr. Rev., June 1, 2005; 26(4): 504 - 524. [Abstract] [Full Text] [PDF]