1. Expression of KIT, EGFR, HER-2 and tyrosine phosphorylation in undifferentiated thyroid carcinoma: Implication for a new therapeutic approach
- Author
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Tetsuya Murakawa, Tetsuya Tanabe, Takao Tanimoto, Osamu Matsubara, Satoshi Kitahara, and Hitoshi Tsuda
- Subjects
Pathology ,medicine.medical_specialty ,Receptor, ErbB-2 ,Pathology and Forensic Medicine ,Thyroid carcinoma ,chemistry.chemical_compound ,Western blot ,Antigens, Neoplasm ,Cell Line, Tumor ,medicine ,Humans ,RNA, Messenger ,Thyroid Neoplasms ,Epidermal growth factor receptor ,Phosphorylation ,Receptor ,Cell Proliferation ,biology ,medicine.diagnostic_test ,Cell Differentiation ,Tyrosine phosphorylation ,General Medicine ,Protein-Tyrosine Kinases ,Molecular biology ,Carcinoma, Papillary ,DNA-Binding Proteins ,ErbB Receptors ,Gene Expression Regulation, Neoplastic ,Proto-Oncogene Proteins c-kit ,DNA Topoisomerases, Type II ,Ki-67 Antigen ,Real-time polymerase chain reaction ,chemistry ,biology.protein ,Tyrosine ,Immunohistochemistry ,Tyrosine kinase - Abstract
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.
- Published
- 2005