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KIT
Friday 12 December 2003
c-kit; CD117
Definition: The proto-oncogene c-kit / CC117 is a receptor tyrosine kinase recognized to initiate essential signal transduction pathways that transmit biological signals for cellular proliferation, differentiation, and metastasis. Aberrant expression or mutation of c-kit has been shown to be involved in the pathogenesis of many cancers.
See also CD117 | IHCDB |
Expression in cells
c-KIT positive spermatogonia
Expression in tumors (Exemples)
chromophobe renal cell carcinoma (100%)
renal oncocytoma (100%)
adenoid cystic carcinoma
- On cytology, adenoid cystic carcinoma has globular metachromatic PAS positive basement membrane material, myoepithelial and epithelial cells.
- The myoepithelial cells stain positive for CK, p63, calponin, SMA, and S100. The epithelial cells stain for CK, CEA and EMA.
- Adenoid cystic carcinoma is CK7 + / CK20 - and positive for CD117.
- It is the most common tumor of the palate, followed by polymorphous low grade adenocarcinoma, and the second most common malignant salivary neoplasm, after mucoepidermoid carcinoma.
Pathology
KIT activating mutations in
- gastrointestinal stromal tumor (GIST)
- mastocytosis
- testicular germ-cell tumors (TGCT)
Use in diagnosis
Differential diagnosis between chromophobe renal cell carcinoma and the granular variant of clear cell renal cell carcinoma (15832088)
KIT is an independent prognostic marker for pancreatic endocrine tumors. (19574886)
References
Expression in normal cells
Immunohistochemical expression analysis of Cx43, Cx26, c-KIT and PlAP in contralateral testis biopsies of patients with non-seminomatous testicular germ cell tumor. Steiner M, Weipoltshammer K, Viehberger G, Meixner EM, Lunglmayr G, Schöfer C. Histochem Cell Biol. 2011 Jan;135(1):73-81. PMID: 21161545
Expression in tumors
KIT is an Independent Prognostic Marker for Pancreatic Endocrine Tumors: A Finding Derived From Analysis of Islet Cell Differentiation Markers. Zhang L, Smyrk TC, Oliveira AM, Lohse CM, Zhang S, Johnson MR, Lloyd RV. Am J Surg Pathol. 2009 Jul 1. PMID: 19574886
Wang HY, Mills SE. KIT and RCC Are Useful in Distinguishing Chromophobe Renal Cell Carcinoma From the Granular Variant of Clear Cell Renal Cell Carcinoma. Am J Surg Pathol. 2005 May;29(5):640-646. PMID: 15832088
Pathology
germline mutations
- germ-line gain-of-function mutations of c-kit receptor tyrosine kinase (KIT) gene in familial gastrointestinal stromal tumors (GIST)
- somatic gain-of-function mutations of c-kit receptor tyrosine kinase (KIT) gene in sporadic gastrointestinal stromal tumors (GIST)
overexpression in tumors
- colorectal neuroendocrine carcinomas: c-kit overexpression observed in a subset of colorectal neuroendocrine carcinomas (not be mediated by activating mutations) (14657715)
- renal oncocytoma (71%) (15105658)
- renal chromophobe renal cell carcinoma (88%) (15105658)
- medulloblastoma (15547773)
Diagnostic use of CD117
positive diagnosis of renal oncocytoma (71%) (15105658)
positive diagnosis of renal chromophobe renal cell carcinoma (88%) (15105658)
Mutations - Variants
KIT-p.D419del
- A subset of gastrointestinal stromal tumors previously regarded as wild-type tumors carries somatic activating mutations in KIT exon 8 (p.D419del).
References
Druker BJ. STI571 (Gleevec) as a paradigm for cancer therapy. Trends Mol Med. 2002;8(4 Suppl):S14-8. PMID: 11927282