Expression and mutation analysis of the tyrosine kinase c-kit in poorly differentiated and anaplastic thyroid carcinoma.
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.
Broecker-Preuss
M
M
Department of Endocrinology, Division of Clinical Chemistry and Laboratory Medicine, University Hospital Essen, Hufelandstrasse 55, Essen, Germany. martina.broecker@uni-due.de
Sheu
S-Y
SY
Worm
K
K
Feldkamp
J
J
Witte
J
J
Scherbaum
W A
WA
Mann
K
K
Schmid
K W
KW
Schott
M
M
D002277:Carcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D002454:Cell Differentiation; D004252:DNA Mutational Analysis; D006801:Humans; D007150:Immunohistochemistry; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*
D019009:Proto-Oncogene Proteins c-kit