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Expression of KIT, EGFR, HER‐2 and tyrosine phosphorylation in undifferentiated thyroid carcinoma: Implication for a new therapeutic approach
Author(s) -
Murakawa Tetsuya,
Tsuda Hitoshi,
Tanimoto Takao,
Tanabe Tetsuya,
Kitahara Satoshi,
Matsubara Osamu
Publication year - 2005
Publication title -
pathology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
eISSN - 1440-1827
pISSN - 1320-5463
DOI - 10.1111/j.1440-1827.2005.01902.x
Subject(s) - cancer research , tyrosine phosphorylation , phosphorylation , tyrosine kinase , receptor tyrosine kinase , tyrosine , epidermal growth factor receptor , immunohistochemistry , thyroid carcinoma , biology , pathology , cancer , medicine , signal transduction , thyroid , endocrinology , microbiology and biotechnology , biochemistry
The KIT, epidermal growth factor receptor (EGFR) and HER‐2 oncoproteins have tyrosine kinase activity and are molecular targets in human cancer therapy. To clarify the significance of KIT, EGFR, and HER‐2 in undifferentiated thyroid carcinoma (UTC), the expression of these receptors and tyrosine phosphorylation was examined immunohistochemically in resected cases of UTC and papillary thyroid carcinoma (PTC). KIT, EGFR, and HER‐2 were also examined at the protein and mRNA levels in five UTC cell lines. KIT expression (1+), EGFR overexpression (2+/3+), HER‐2 expression (1+), and tyrosine phosphorylation were detected immunohistochemically in 40%, 70%, 10%, and 50% of the 10 UTC. In 20 PTC, KIT, EGFR, and HER‐2 were not detected, but tyrosine phosphorylation was detected in 25% of cases. In the five UTC cell lines, KIT expression (1+), EGFR overexpression (3+), HER‐2 expression (1+), and tyrosine phosphorylation were detected immunocytochemically in 60%, 100%, 20%, and 40%, respectively. Western blot analysis did not detect KIT expression, but did detect EGFR and HER‐2 expression in all five cell lines. Real‐time polymerase chain reaction detected KIT mRNA in two of the cell lines (40%), EGFR in five (100%), and HER‐2 in three (60%). The present findings suggest that EGFR overexpression was involved in the proliferation and development of UTC and was frequently accompanied by tyrosine phosphorylation. Expression of KIT and HER‐2 appeared to be weak but significant, suggesting a possible role in the development of UTC. Molecular therapies targeting KIT, EGFR, HER‐2, and/or tyrosine phosphorylation might be indicated for UTC.