CD117 (c-kit) is a transmembrane protein that functions as a tyrosine kinase receptor.
The gene is KIT, the protein is c-KIT. There are several mutational loci associated with GIST (see chart below). This is of importance, because primary exon 9 mutations and secondary (acquired after initial treatment) exon 13 mutations are associated with resistance to Imatinib (a tyrosine kinase inhibitor). In these cases you must use very high doses of Imatinib, or a new agent called Sunitinib. KIT and PDGFRa mutations in GISTs thumb|left|400px|link=File:Sutent_IndicationGIST_PrimaryMutation.gif(mutually exclusive)
- Membranous: some tumors, including seminoma
- Cytoplasmic: GIST
- Golgi ("perinuclear dot-like"): GIST, seminoma
- Luminal surface: adenoid cystic carcinoma
Expression in Normal TissuesEdit
- Mast Cells
- Interstitial Cells of Cajal (in muscularis propria of GI tract)
- Myeloid Blasts in Bone Marrow
Expression in Neoplastic EntitiesEdit
- High risk gastrointestinal stromal tumors (GIST)
- Acute Myelogenous Leukemia (also myeloid sarcoma)
- Adenoid cystic carcinoma (stains luminal surface membrane. Does not stain myoepithelial cells.)
- Polymorphous low grade adenocarcinoma
- Basal cell adenocarcinoma
- Pleomorphic Undifferentiated Sarcoma (previously known as MFH)(occasional cases)
- Melanoma (occasionally)
- Small cell carcinoma.
- Granulocytic sarcoma.
- Low risk gastrointestinal stromal tumors (GIST)
- Mastocytosis/Mast Cell Disease
- Monomorphic adenoma (basal cell)
Expression in Non-Neoplastic EntitiesEdit
Practical Uses / PanelsEdit
- In spindle cell tumors of GI tract, this panel is very useful:
- Smooth Muscle Actin (SMA) (positive in leiomyoma and leiomyosarcoma, occasionally in GIST)
- S100 Protein (positive in schwannoma)
- CD117 (ckit) (positive in GIST)
- CD34 (usually positive in GIST...useful in identifying CD117 negative GISTs)
- Alternatively, you can consider replacing CD117 and CD34 with DOG1 (a very sensitive and specific marker for GIST).
This antigen is typically NOT expressed by the following entities: