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Updated: Jul 3, 2026
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Expression and mutation analysis of the tyrosine kinase c-kit in poorly differentiated and anaplastic thyroid
M Broecker-Preuss1, S-Y Sheu, K Worm
1Department of Endocrinology, Division of Clinical Chemistry and Laboratory Medicine, University Hospital Essen, Hufelandstrasse 55, Essen, Germany. martina.broecker@uni-due.de
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.
Insights
Imatinib mesylate targets c-kit, but this study found no c-kit expression or mutations in anaplastic thyroid carcinoma. Therefore, c-kit is unlikely to be a therapeutic target in these aggressive thyroid cancers.
Area of Science:
- Oncology
- Molecular Biology
- Pathology
Background:
- Poorly differentiated and anaplastic thyroid carcinomas are aggressive and resistant to conventional treatments.
- Imatinib mesylate is a tyrosine kinase inhibitor effective against various cancers by targeting molecules like c-kit.
- Investigating c-kit expression and mutations is crucial to determine imatinib's potential efficacy in thyroid cancer.
Purpose of the Study:
- To assess c-kit expression and mutations in anaplastic and poorly differentiated thyroid carcinoma.
- To compare c-kit expression with differentiated thyroid carcinoma and adenoma.
- To evaluate the role of c-kit in thyroid carcinoma proliferation and its potential as a therapeutic target.
Main Methods:
- Immunohistochemistry was used to analyze c-kit expression in 224 thyroid tissue samples.
- Mutation analysis of c-kit gene exons 9, 11, 13, and 17 was performed in aggressive thyroid carcinoma subtypes.
- Comparison of c-kit expression across different thyroid tumor types, including adenoma and differentiated carcinoma.
Main Results:
- c-Kit expression was absent in all anaplastic thyroid carcinomas analyzed.
- Poorly differentiated thyroid carcinomas showed variable c-kit expression, with higher intensity in areas with differentiated features.
- No mutations were detected in the analyzed exons of the c-kit gene in any of the aggressive thyroid tumors.
Conclusions:
- The lack of c-kit expression and mutations in undifferentiated thyroid carcinomas suggests it is not a primary driver of proliferation.
- c-Kit is unlikely to be a significant therapeutic target for imatinib mesylate in anaplastic thyroid carcinoma.
- Further research is needed to identify alternative molecular targets for imatinib in dedifferentiated thyroid carcinoma.
