CD117

CD117, encoded by the KIT gene on chromosome 4q11-12, is a transmembrane receptor essential for the development and proliferation of mast cells, melanocytes, and interstitial cells of Cajal, with the latter being critical for gastrointestinal motility. CD117 typically shows a distinct  membranous staining reaction, often accompanied by a coexisting cytoplasmic staining reaction. CD117 is also expressed in a variety of other types of normal cells, including epithelium of breast, sweat and salivary glands, germ cells, hematopoietic stem cells, including immature myeloid cells, epithelial cells of renal tubules, and thyroid follicular cells. Notably, CD117 is absent in smooth muscle cells, mature lymphocytes, and most endothelial cells, though it can be expressed in endothelial cells within neovascular structures.

CD117 is central for diagnostics of gastrointestinal stromal tumors (GISTs) and mast cell neoplasms, as well as identification of myeloid stem cells for myelodysplastic syndrome and acute myeloid leukemia. 

Moreover, CD117, in combination with vimentin, is used to differentiate renal tumors: proximal tubule neoplasms, such as clear cell and papillary carcinomas, are CD117-negative/vimentin-positive, while distal tubule neoplasms, such as chromophobe carcinoma and oncocytoma, are CD117-positive/vimentin-negative.

Due to its widespread expression across various tissues, CD117 is not recommended for inclusion in diagnostic panels for tumors of unknown primary origin.

• Diagnosis of GISTs and mast cell neoplasms.
• Distinguishing GISTs (CD117-positive) from smooth muscle tumors (CD117-negative).
• Diagnosis of myeloid lesions.
• Differentiation of renal tumors: proximal vs. distal tubule neoplasms.

Appendix or colon is recommended for use as both positive and negative tissue controls for CD117. Virtually all mast cells must show a strong predominantly membranous staining reaction and Cajal cells at least moderate and distinct membranous staining reaction. In both cell types a coexisting cytoplasmic staining reaction typically will be seen. No staining reaction in the smooth muscle cells of the lamina muscularis propria or in the smooth muscle cells surrounding the vessels should be seen.  Note that a weak to moderate staining reaction of neovascular structures (endothelium) and epithelial cells lining the basal compartment of the crypts should be expected by protocols providing a high level of analytical sensitivity for CD117.