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Dissecting molecular events in thyroid neoplasia provides evidence for distinct evolution of follicular thyroid adenoma and carcinoma.
Clinic for Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany.
Clinic for Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany.
Clinic for Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany.
Department of Pharmaceutical Chemistry and Bioanalytics, Martin Luther University of Halle- Wittenberg, Halle-Wittenberg, Germany.
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2011 (English)In: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 179, no 6, 3066-74 p.Article in journal (Refereed) Published
Abstract [en]

Benign hypofunctional cold thyroid nodules (CTNs) are a frequent scintiscan finding and need to be distinguished from thyroid carcinomas. The origin of CTNs with follicular morphologic features is unresolved. The DNA damage response might act as a physiologic barrier, inhibiting the progression of preneoplastic lesions to neoplasia. We investigated the following in hypofunctional follicular adenoma (FA) and follicular thyroid cancer (FTC): i) the mutation rate of frequently activated oncogenes, ii) the activation of DNA damage response checkpoints, and iii) the differential proteomic pattern between FA and FTC. Both FTC and FA, which did not harbor RAS, phosphoinositide-3-kinase, or PAX/peroxisome proliferator activated receptor-γ mutations, express various proteins in common and others that are more distinctly expressed in FTC rather than in FA or normal thyroid tissue. This finding is in line with the finding of constitutive DNA damage checkpoint activation (p-Chk2, γ-H2AX) and evidence for replicative stress causing genomic instability (increased cyclin E, retinoblastoma, or E2F1 mRNA expression) in FTC but not FA. We discuss the findings of the increased expression of translationally controlled tumor protein, phosphatase 2A inhibitor, and DJ-1 in FTC compared with FA identified by proteomics and their potential implication in follicular thyroid carcinogenesis. Our present findings argue for the definition of FA as a truly benign entity and against progressive development of FA to FTC.

Place, publisher, year, edition, pages
2011. Vol. 179, no 6, 3066-74 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-101894DOI: 10.1016/j.ajpath.2011.08.033PubMedID: 21983636OAI: diva2:666783
Available from: 2013-11-24 Created: 2013-11-24 Last updated: 2013-11-24

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Gimm, Oliver
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