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Test Available
The proto-oncogene c-kit, located on chromosome 4, produces the transmembrane glycoprotein KIT (CD117). KIT is closely related to the platelet-derived growth-factor receptor (PDGFR), and is involved in cell differentiation. Expression of c-kit has been detected in several malignancies such as gastrointestinal stromal tumors (GIST), lymphomas, melanomas, germ cell tumors, lung cancers, and ovarian cancers. Most GISTs contain a gain of function mutation in the c-kit proto-oncogene which induces cellular proliferation. This has allowed for development of targeted molecular therapy which inhibits KIT. This has revolutionized the treatment of patients with GISTs. The success of the targeted therapy proves that a specific inhibitor can counteract the effects of a genetic defect that cause neoplasia. Overexpression of the KIT protein has important prognostic and therapeutic implications for a number of malignancies. Immunohistochemistry is used to evaluate c-kit overexpression in order to find tumors that may respond to targeted therapy that inhibits KIT. For more information on c-kit testing by IHC, please contact Dr. Raheela Ashfaq at Veripath OncoDiagnostics at 214-590-8042 orRaheela.Ashfaq@UTSouthwestern.edu.
Selected references:
1. Janice V. Scobie; Geza Acs, M.D., Ph.D.; Christina A. Bandera, M.D.; Stephanie V. Blank, M.D.; James E. Wheeler, M.D.; Teresa L. Pasha; Marilyn Salscheider; Paul J. Zhang, M.D. C-Kit Immunoreactivity in Endometrial Adenocarcinomas and Its Clinicopathologic Significance. International Journal of Gynecological Pathology 2003; 22(2):149-155
2.Andrew E. Horvai, M.D., Ph.D., Li Li, Ph.D., Zhidong Xu, Ph.D., Miranda J. Kramer, R.N., M.S., David M. Jablons, M.D. and Patrick A. Treseler, M.D., Ph.D. c-Kit Is Not Expressed in Malignant Mesothelioma Modern Pathology 16:818-822 (2003)
3.Michael C. Heinrich, Charles D. Blanke, Brian J. Druker, Christopher L. Corless Inhibition of KIT Tyrosine Kinase Activity: A Novel Molecular Approach to the Treatment of KIT-Positive Malignancies. Journal of Clinical Oncology, Vol 20, Issue 6 (March), 2002: 1692-1703
4.Hornick J, Fletcher C. Validating immunohistochemical staining for KIT (CD117). Am J Clin Pathol 2003 Mar ; 119(3): 325-7
5.DeMatteo RP.The GIST of targeted cancer therapy: a tumor (gastrointestinal stromal tumor), a mutated gene (c-kit), and a molecular inhibitor (STI571). Ann Surg Oncol. 2002 Nov;9(9):831-9. |
