CD117 (c-kit) is a member of the type III tyrosine kinase receptor family, and is a transmembrane protein.  Immunohistochemical expression of CD117 can be seen in many different normal tissue components (e.g. mast cells) and neoplastic tissues.  Therefore, CD117 should be used in a careful targeted manner; usually as part of a larger panel.  Limitations of specificity should always be kept in mind.

CD117 is most often used as a myeloblast marker in bone marrow biopsies, and to identify GISTs.  It is important to understand what else may stain with CD117 (bright staining of mast cells in BM bxs., compared to dim staining of blasts), so one does not misinterpret the expression pattern.  Erythroid precursor cell may also express CD117, which may cause confusion when evaluating for myeloblast percentage.  Ohgami recommends using CD117, E-cadherin, and CD34 in combination in this situation.  CD71 (erythroid precursor marker) may also be helpful.

CD117 has been found to be expressed in 71-100% of oncocytomas and 83-100% of chromophobe renal cell carcinomas with other subtypes of renal cell carcinoma being non-reactive.  Therefore, CD117 may be a useful part of a larger panel (e.g. RCCMa, CD10, Vimentin, and cytokeratin) to diagnosis and subtype renal tumors (especially granular cell variant of RCC vs. chromophobe RCC or oncocytoma).

Approximately 95% of gastrointestinal stromal tumors (GIST) will react with CD117 by immunohistochemistry.  It is important to emphasize that CD117 expression does not necessarily correlate with response to imatinib therapy (tyrosine kinase inhibitor).  Lack of reactivity with CD117 should not exclude a patient from imatinib therapy.  CD117 negative (kit-negative) GIST often contain PDGFRA mutations, which may be sensitive to imatinib.  Sometimes weak expression of CD117 may be seen in non-GIST tumors, and this marker should be used as part of a larger panel incorporating the differential diagnosis (e.g. S-100, Desmin, CD34).  DOG-1 antibody may be expressed in CD117 negative GIST cases, which may serve as an alternative marker.

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