CD117

Synonyms: c-kit, tyrosine-protein kinase KIT, mast/stem cell growth factor receptor (SCFR)

by Jan Klos

Background

CD117 is a cell membrane protein (encoded on chromosome 4q11-12) with the receptor function for stem cell factor (SCF). CD117 shows tyrosine kinase activity and is essential for survival and function of mast cells, hematopoietic stem cells, melanocytes, germ cells and interstitial cells of Cajal. Weaker expression is also found on several types of epithelial cells including breast, sweat glands and salivary glands, renal tubular cells, thyroid follicular cells, testicular and ovarian interstitial cells, neurons of the central nervous system

Staining in normal cells

Interstitial cells of Cajal, hematopoietic progenitor cells, melanocytes, embryonic/fetal brain, endothelium, gonads, mast cells, breast epithelium, and germ cells are stained positive.

Staining in tumors

There is a long list of tumors including carcinomas which stain positive for CD117. The most common and most important are as follows: gastrointestinal stromal tumor (GIST) and its` variants, myeloid proliferations (AML, CML, granulocytic sarcoma), mast cell proliferations, germ cell tumors (seminomas /dysgerminomas) and chromophobe renal cell carcinoma. Around 40-50% of angiomyolipomas,  angiosarcomas, clear cell sarcomas,  epithelioid sarcomas, Ewing sarcomas, melanoma,  osteosarcoma, rhabdomyosarcoma, sclerosing mesenteritis (variable), small cell lung cancer, adenoid cystic carcinoma of salivary gland (staining of epithelial component). Reported positive staining in some cases of intraabdominal (mesenteric) fibromatosis depends on antibody used or applied protocol and is not correlated to mutations in CD117.

Staining pattern

Staining pattern is cytoplasmic with strong accentuation along the cell membranes. Weaker staining may be only cytoplasmic.

Control tissue

Appendix where optimal staining should demonstrate strongly stained positive Cajal cells, mast cells, and neovascular structures. No staining of the smooth muscle cells in lamina muscularis propria or smooth muscle cells surrounding the vessels should be seen.

Application

  • Classification of mesenchymal tumors of the gastrointestinal tract (including the mesentery) particularly GIST. Identification of tumors as GIST is important since pharmacological inhibition of tyrosine phosphorylation is effective in the treatment of these tumors. Recommended to use in panel together with CD34, S-100, alpha-smooth muscle actin and desmin.
  • Classification of germ cell tumors, as seminoma/dysgerminoma stains in the absolute majority of cases, showing a strong membranous staining, while embryonal carcinoma stains in about 50% of cases, with a weaker, mostly membranous reaction. Recommended to use in panel with CD30 when differentiating seminoma from embryonal carcinoma.
  • Identification of in situ component (ITGCN, GCNIS) of germ cell tumors
  • Identification of mast cells and their proliferation.
  • As a part of the panel used for identification of myeloid proliferation.
  • Positive staining of Giardia lamblia trophozoites in biopsies is useful confirming suspected infection.

Selected references

  1. Hornick JL,  Fletcher ChDM. The significance of KIT (CD117) in gastrointestinal stromal tumors. Int J Surg Pathol. 2004 Apr;12(2):93-7. doi: 10.1177/106689690401200201.  PMID: 15173913 DOI: 10.1177/106689690401200201 
  2. Lee JR1, Joshi V, Griffin Jr JW, et al. Gastrointestinal Autonomic Nerve Tumor: Immunohistochemical and Molecular Identity With Gastrointestinal Stromal Tumor. Am J Surg Path. 2001 Aug;25(8):979-87. doi: 10.1097/00000478-200108000-00001. 
  3. Miettinen M1, Sobin LH, Sarlomo-Rikala M. Immunohistochemical Spectrum of GISTs at Different Sites and Their Differential Diagnosis With a Referhttps://pubmed.ncbi.nlm.nih.gov/11048809/ence to CD117 (KIT). Mod Pathol.. 2000 Oct;13(10):1134-42.  doi: 10.1038/modpathol.3880210.PMID: 11048809.
  4. Montgomery E1, Torbenson MS, Manju Kaushal M, et al. Beta-catenin Immunohistochemistry Separates Mesenteric Fibromatosis From Gastrointestinal Stromal Tumor and Sclerosing Mesenteritis. Am J Surg pathol. 2002 Oct;26(10):1296-301.  doi: 10.1097/00000478-200210000-00006 PMID:12360044 https://pubmed.ncbi.nlm.nih.gov/11048809/ 
  5. Naeem M 1, Dahiya M, Clark J.I, et al. Analysis of C-Kit Protein Expression in Small-Cell Lung Carcinoma and Its Implication for Prognosis. Hum Path.2002 Dec;33(12):1182-7. doi: 10.1053/hupa.2002.129199. PMID: 12514786.
  6. Pernick N. CD117. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/cdmarkerscd117.html. Accessed June 27th, 2020.
  7. Sinelnikov I 1, Sion-Vardy N, Shaco-Levy R. C-kit (CD117) immunostain is useful for the diagnosis of Giardia lamblia in duodenal biopsies Hum Pathol. 2009 Mar;40(3):323-5.  doi: 10.1016/j.humpath.2008.07.015. Epub 2008 Oct 5. PMID: 18835628DOI: 10.1016/j.humpath.2008.07.015