CD117, also known as c-Kit or KIT, is a protein located on the surface of various cells throughout the human body. This protein functions as a receptor, meaning it receives signals from outside the cell and transmits them inward. These signals play a role in directing cellular activities.
The Biological Role of CD117
CD117 acts as a receptor tyrosine kinase, binding to a specific substance called stem cell factor (SCF). When SCF attaches to CD117, it triggers a process where the receptor forms a dimer and activates its internal signaling components. This activation then initiates a cascade of signals within the cell, influencing various cellular functions such as growth, division, and survival.
It plays a role in the development and maintenance of several cell types. It is found on hematopoietic stem cells, which form blood cells in the bone marrow. Mast cells, involved in allergic reactions, also express CD117, as do melanocytes, the pigment-producing cells in the skin. Furthermore, CD117 is present on the interstitial cells of Cajal, which serve as pacemaker cells regulating movement in the digestive system.
CD117 as a Diagnostic Marker in Disease
Pathologists use the presence or absence of CD117 to identify and categorize certain diseases, particularly cancers. Some cancer cells retain the CD117 marker from their originating cell type, aiding diagnosis. This makes CD117 a useful identifier in distinguishing specific tumor types from others that may appear similar under a microscope.
CD117 positivity is a characteristic feature in several medical conditions. Gastrointestinal stromal tumors (GISTs), common mesenchymal tumors of the digestive tract, show CD117 expression in approximately 95% of cases. It is also frequently found in acute myeloid leukemia (AML), with positivity in a high percentage of cases. Mastocytosis, a disorder of abnormal mast cell accumulation, also uses CD117 expression as a key diagnostic criterion. Additionally, CD117 is expressed in certain types of testicular cancer known as seminomas and in some melanomas, aiding in their classification.
The Process of CD117 Testing
CD117 detection in tissue samples typically involves immunohistochemistry (IHC). This process begins with obtaining a small tissue sample, often via biopsy. The tissue is then carefully prepared and embedded in paraffin wax to create thin sections for microscopic examination.
Specific antibodies that bind to CD117 are then applied to these tissue sections. A chemical reaction follows, which makes these bound antibodies visible under a microscope, often appearing as a brown or red stain. A “positive” result indicates the presence of the CD117 protein on the surface of the cells in the sample, while a “negative” result means the protein was not detected. This visual evidence helps pathologists confirm or refine a diagnosis based on the cellular characteristics observed.
Therapeutic Implications of CD117
In some cancers, a genetic alteration in the KIT gene, which codes for the CD117 protein, leads to uncontrolled cell growth. This mutation can cause CD117 to become continuously active, signaling the cell to grow and divide without proper regulation. Such “switched on” activity of CD117 is a significant factor in the progression of certain tumors, including a large majority of GISTs.
Targeted therapies address this overactivity. Tyrosine kinase inhibitors (TKIs), such as imatinib (Gleevec), block the hyperactive CD117 protein. By inhibiting the abnormal signaling from CD117, these medications can stop the cancer cells from growing and dividing. This approach has transformed the management of conditions like GIST, where imatinib has shown considerable effectiveness in patients with CD117-positive tumors.