Expression And Significance Of C-kit Receptor In Osteosarcoma

Aims: c-kit receptor (CD117) is a transmembrane tyrosine kinase receptor which is encoded by the proto-oncogene c-kit. The tyrosine kinase receptor can be activated by mutation of the c-kit gene. These mutations result in ligand-independent kinase activity with consequent receptor autophosphorylation .It causes certain types of cells to grow, proliferate and differentiate. Altered forms of this receptor may be associated with proliferation and anti-apoptosis of tumor cells. Overexpression of CD117 in many tumors has previously been documented be associating with development of tumor,especially gastrointestinal stromal tumor. However, few studies have addressed the expression of CD117 in the osteosarcoma. To investigate the expression of c-kit in human osteosarcoma and their relationships with clinicopathological parameters and prognostic value. At the same time, because of some tumors highly expressed c-kit respond to imatinib mesylate—a tyrosine kinase inhibitor, our investigation was performed to determine mutational status of exons 11 and 17 of c-kit in osteosarcomas. Methods:The expression of C-kit was measured in 40 human osteosarcoma and 10 fibrous dysplasia by immunohistochemistry and its relationship to prognosis was analyzed statistically.And then, DNA were extracted, polymerase chain reaction (PCR) amplification of exons 11 and 17, single-strand conformational polymorphism (SSCP), and DNA sequencing to detect the presence of mutation(s). Results:1) The expression rate of c-kit in conventional osteosarcoma was 62.5%. The conventional osteosarcoma with highly expression of c-kit was prone to recur locally. The survival time after operation of the patients with c-kit highly expression were significantly lower than that of the patients with c-kit lowly expression.2) Sequence of exon 11 and exon 17 in osteosarcoma were amplified successfully.3) No mutation in exon 11 and exon 17 was founded in 38 osteosarcoma and DNA sequencing also didn't detect the presence of mutation(s). Conclusions:The expression of CD117 has a definite value in judging prognosis in osteosarcoma. No mutation in exon 11 and exon 17 was founded in 38 osteosarcoma .The mutation of exons is low probability.Our experiment results show that the use of tyrosine kinase inhibitor in treatment of osteosarcoma is possible. However, the use of Imatinib mesylate in therapy should be deeply researched.