CD117 is a 145-160 kDa cell membrane protein encoded by the c-kit proto-oncogene (chromosome 4q11-12). The protein is a type III tyrosine kinase growth factor receptor* for stem cell factor (SCF), also known as mast cell growth factor. CD117 is required for the development and growth of a large number of cells expressing this protein. CD117 is expressed in mast cells, melanocytes and interstitial cells of Cajal (ICC)**. The cells (particularly the mast cells) show a strong membrane as well as cytoplasmic staining. CD117 moreover is expressed in various epithelia (breast, sweat glands and salivary glands, renal tubular cells, thyroid follicular cells), usually showing a weaker, cytoplasmic reaction. CD117 is also demonstrated in testicular and ovarian interstitial cells, in neurons of the central nervous system (cerebellum, hippocampus, and dorsal horn of the spinal cord), and in immature myeloid cells (at low levels, approximately 70% of CD34+ cells in normal bone marrow as demonstrated by flow cytometry). Finally CD117 is detected in trophoblastic cells, foetal (but not mature) endothelial cells and foetal (but not mature) basal cells of the skin. CD117 does not occur in smooth muscle cells. * Family of transmembrane proteins essential for the regulation of cell growth and maintenance. When a growth factor is bound to its receptor, the latter is phosphorylated and begins a cascade of intracytoplasmic signals. ** Cells involved in the generation of electrical pacemaker activity for gastrointestinal motility. The cells are considered to be the origin of gastrointestinal stromal tumours.
The following neoplasms express CD117 in more than 90% of the cases*: Gastrointestinal stromal tumour (GIST), mast cell neoplasms, malignant melanoma (however, the expression of CD117 is lost during progression and metastasising), seminoma/dysgerminoma and intratubular germ cell neoplasia, endometrial carcinoma, follicular and papillary thyroid carcinoma, Merkel cell carcinoma, cylindroma, malignant glioma, and angiomyolipoma. The following express CD117 in 50-90% of the cases: adenocarcinomas of lung and pancreas, hepatocellular carcinoma, squamous cell carcinoma of esophagus and lung, transitiocellular carcinoma, endodermal sinus tumour, neuroblastoma, osteogenic sarcoma, fibromatosis, Wilms' tumour, and epithelioid sarcoma. The following express CD117 in 10-50% of the cases: adenocarcinomas of breast, salivary glands, ovary, colorectum and prostate, small cell carcinoma, embryonal carcinoma, malignant mesothelioma, Ewing sarcoma, synovial sarcoma, chondrosarcoma, angiosarcoma and Kaposi sarcoma, malignant phyllodes tumour, perineurioma, acute myeloid leukaemia and subtypes of malignant lymphomas. The staining pattern in strongly CD117 positive neoplasms is generally diffuse/granular cytoplasmic with membrane accentuation. Occasionally, a perinuclear staining is seen. In neoplasms with a weaker expression, this is mostly cytoplasmic. CD117 is not detected in smooth muscle tumours, rhabdomyosarcoma, schwannoma (except for the melanotic subtype), peripheral nerve sheath tumour, endometrial stromal sarcoma, desmoplastic small cell tumour, and solitary fibrous tumour. * The grouping of neoplasms based on the proportion in which a certain epitope is expressed should be considered as a guideline only as it is based on metaanalyzes of studies using different study materials and methodologies (antibodies, epitope retrieval methods etc.)
CD117 is of great importance for the classification of mesenchymal tumours of the gastrointestinal tract (including the mesentery). A newly developed molecule, STI-571 (Gleveec), binds selectively to CD117 resulting in inhibition of tyrosine phosphorylation. This molecule has shown effective in the treatment of GIST, enhancing the importance of using the CD117 antibody for tumour classification and section for therapy. In the immunohistochemical classification of gastrointestinal tumours, the antibody panel should include CD34, S-100 protein, alpha-smooth muscle actin, and desmin. CD117 may also be used for classification of germinal cell tumours, as seminoma/dysgerminoma stains in the majority of cases, showing a strong membranous staining, while embryonal carcinoma stains in a small proportion of cases, with a weaker, membranous reaction. An panel for distinguishing seminoma from embryonal carcinoma should include CD30. Also in the identification of mast cell neoplasms CD117 has a potential.
Appendix is recommended as positive and negative tissue controls for CD117. Cajal cells, mast cells and neovascular structures must be stained as strong as possible without any staining reaction of the smooth muscle cells in lamina muscularis propria or smooth muscle cells surrounding the vessels.
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