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Horm Metab Res 2008; 40(10): 685-691
DOI: 10.1055/s-2008-1080895
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Expression and Mutation Analysis of the Tyrosine Kinase c-Kit in Poorly Differentiated and Anaplastic Thyroid Carcinoma

M. Broecker-Preuss 1 [*] , S.-Y. Sheu 2 [*] , K. Worm 2 , J. Feldkamp 3 , J. Witte 4 , W. A. Scherbaum 5 , K. Mann 1 , K. W. Schmid 2 , M. Schott 5
  • 1Department of Endocrinology, Division of Clinical Chemistry and Laboratory Medicine, University Hospital Essen, Essen, Germany
  • 2Institute of Pathology and Neuropathology, University Clinic Essen, Essen, Germany
  • 3Department of Internal Medicine, Municipal Hospital Bielefeld, Bielefeld, Germany
  • 4Department of Surgery, Municipal Hospital Wesseling, Wesseling, Germany
  • 5Department of Endocrinology, Diabetes and Rheumatology, University Hospital Düsseldorf, Düsseldorf, Germany
Further Information

Publication History

received 19.12.2007

accepted 10.03.2008

Publication Date:
11 July 2008 (online)

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Abstract

Poorly differentiated and anaplastic thyroid carcinoma are aggressive tumors failing to res-pond to conventional therapy. Imatinib mesylate offers an effective therapeutic option in patients with various types of malignancies by inhibiting tyrosine kinases such as c-kit. In this study we investigated c-kit expression in anaplastic and poorly differentiated thyroid carcinoma compared to differentiated carcinoma and adenoma and the presence of c-kit mutations. In total, 224 thyroid tissues were analyzed by immunohistochemistry. Mutation analysis of exon 9, 11, 13, and 17 of the c-kit gene was performed in anaplastic and poorly differentiated carcinoma. c-Kit expression was negative in all anaplastic thyroid carcinoma, while c-kit expression of poorly differentiated carcinoma showed a high variability with a more intense staining in tumors showing obvious differentiated malignant follicular tumor areas. Differentiated carcinoma showed a slight, but not significantly stronger c-kit expression than poorly differentiated carcinoma. All tumors revealed wild type sequences of c-kit gene in exons 9, 11, 13, and 17. The low or lacking c-kit expression in undifferentiated thyroid carcinoma together with the lack of mutations argue against a crucial role of c-kit in thyroid carcinoma cell proliferation. Further molecular targets of imatinib mesylate have to be analyzed to estimate a potential benefit of this drug for patients with dedifferentiated thyroid carcinoma.

Key words

tyrosine kinase inhibitor - c-kit expression - c-kit mutation - undifferentiated thyroid carcinoma - imatinib

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1 These authors contributed equally to this work.
M. S. was supported by the American Thyroid Association (ThyCa).

Correspondence

M. Broecker-PreussPh.D 

Department of Clinical Chemistry and Laboratory Medicine

University Hospital Essen

Hufelandstr. 55

45122 Essen

Germany

Phone: +49/201/723 50 48

Fax: +49/201/723 50 58

Email: martina.broecker@uni-due.de

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