Overview of Therapeutic Biomarkers in Cancer
Sherry X. Yang, Janet E. Dancey in Handbook of Therapeutic Biomarkers in Cancer, 2021
c-Kit or CD117, encoded by the KIT gene, is a cytokine receptor expressed on the cell membrane of hematopoietic stem cells and other cell types (Chapter 9). Mutations in the KIT gene and PDGFRA are found in about 85% and 10% of gastrointestinal stromal tumors (GIST), respectively, and some in other types of tumors. Imatinib is indicated for patients with KIT-positive unresectable and/or metastatic malignant GIST as well as adjuvant therapy of adult patients after resection of KIT-positive GIST [38]. The mutations-negative GIST tumors are in general resistant to imatinib therapy. In early 2020, the FDA approved avapritinib for adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including D842V mutations. It is the first therapy approved for patients with unresectable and metastatic malignant GIST harboring a PDGFRA exon 18 mutation.
Mastocytosis
Dongyou Liu in Tumors and Cancers, 2017
Mastocytosis is linked to mutations in KIT located on a 21-exon containing gene on chromosome 4q12, which encodes a 976 amino acid protein with a molecular weight of 145 kDa. Expressed by hematopoietic stem/progenitor cells, germ cells, melanocytes, and interstitial cells of Cajal, this protein functions as a type III tyrosine kinase transmembrane receptor (CD117). The ligand for KIT receptor, stem cell factor (SCF), or KIT ligand induces and regulates the development, proliferation, maturation, survival, and mediator release from mast cells. Mutations in the KIT gene lead to a gain-of-function receptor and result in uncontrolled proliferation, enhanced survival, accumulation and degranulation of mast cells, and subsequent infiltration of various tissues. KIT gene mutation (especially D816V) is detected in more than 80% of all systemic mastocytosis cases (>90% in indolent and >70% in advanced disease) [3–5].
Flow Cytometry
Wojciech Gorczyca in Atlas of Differential Diagnosis in Neoplastic Hematopathology, 2014
Myeloblasts are positive for CD34, CD38, HLA-DR, CD117, CD4, CD13 (dim), and CD33 (CD34 is expressed by all hematopoietic precursors, including early myeloblasts; CD117 expression appears after CD34). The expression of CD13 appears first, followed by acquisition of CD33 and increased expression of both CD13 and CD33. Promyelocytes lose CD34 and HLA-DR, retain CD117, and show a positive expression of CD13 and CD33 (bright). They show a dim expression of CD4 and start to acquire CD15. At the transition to myelocytes, the expression of CD117 is lost. Myelocytes start to acquire the expression of CD11b and its intensity increases as the cells mature to late myelocytes and metamyelocytes (at the same time, the expression of CD4 disappears). CD33 expression progressively decreases. Metamyelocytes start to express CD10 and CD16, which increase in the intensity as the cells progress to mature neutrophils. Segmented forms display bright expression of CD11b, CD11c, CD10, CD16, and CD15. Other markers expressed at metamyelocytic/band/segmented stages include CD24, CD32, CD35, and CD65. Minute subset of normal granulocytes shows a dim expression of CD64. Expression of CD14 and CD64 is upregulated in infections and patients on granulocyte colony-stimulating factor (G-CSF) therapy. Among glycosylphosphatidylinositol-anchored proteins (GPI-APs), CD55 and CD59 are constantly expressed along all the different stages of maturation; no significant differences are detected for CD59, but the expression of CD55 decreases from the early precursors to promyelocytes, and then increases along the maturation toward mature neutrophils. Figure 3.61 shows the expression of CD10, CD11b, CD11c, CD16, and HLA-DR during normal myeloid maturation.
Progress in determining response to treatment in gastrointestinal stromal tumor
Published in Expert Review of Anticancer Therapy, 2020
Junaid Arshad, Jibran Ahmed, Ty Subhawong, Jonathan C Trent
GIST originates from the interstitial cells of Cajal, which share morphologic and immunophenotypic similarities with these tumors. These cells stain for vimentin and are immunoreactive for KIT (CD117) and CD34, whereas they typically lack a myoid or schwannian immunophenotype (e.g. S100) [4]. CD117 is a product of the c-kit proto-oncogene expression. On immunohistochemistry (IHC), CD117 and DOG1 (ANO1/TMEM16A) are most specific for GIST and help to differentiate these from other tumor types [5]. CD34 is positive on IHC in 70% of cases of GIST [6], varying from 47% in the small bowel to 96–100% in rectum and esophagus [7]. CD34 is, however, also expressed by cells in tumors of fibroblastic and endothelial origin. CD117, on the other hand, is expressed by 85% of cells of malignant GIST, both spindle cell and epithelioid subtypes. Other mesenchymal GI tumors (leiomyoma, leiomyosarcoma, and schwannomas) do not usually express CD117 [8]. In a small subset of tumors that are wild-type for KIT and PDGFRA, succinate dehydrogenase (SDH) may be deficient through deletion or epigenetic repression [9].
Neonatal Gastrointestinal Stromal Tumor of the Sigmoid Colon: A Case Report and Review of Literature
Published in Fetal and Pediatric Pathology, 2020
Mostafa Kotb, Marwa Abdelaziz, Marwa Beyaly, Mohamed Mekawy, Hayssam Rashwan, Nagwa Mashali
Other spindle cell neoplasms that can be seen in the GIT include smooth muscle tumors, inflammatory myofibroblastic tumor and tumors of neural origin- namely schwannoma. [14] Tumors of smooth muscle origin (leiomyoma/leiomyosarcoma) are expected to be diffusely and strongly positive for SMA; thus, were excluded based on the focal expression of SMA in the present case. Inflammatory myofibroblastic tumor (IMT) was excluded since the tumor did not show the classic histological picture of IMT which entails the presence of an inflammatory infiltrate rich in lymphocytes and plasma cells along with a spindled population composed of plump myofibroblasts disposed against a loose myxoid stroma or less commonly a hyalinized stroma. Additionally, the neoplastic cells were negative for ALK1. [15] Moreover, intrabdominal IMTs patients often have systemic manifestations as fever and night sweats [14] which were absent in our case. Schwannoma was also excluded based on the negative staining of tumor cells for S100 which is known to be strong and diffusely positive in schwannoma. None of the aforementioned tumors is known to express CD117. [15]
Investigation of apoptotic and antiproliferative effects of Turkish natural tetraploids Trifolium pratense L. extract on C6 glioblastoma cells via light and electron microscopy
Published in Ultrastructural Pathology, 2023
Gamze Tanrıverdi, Aynur Abdulova, Hatice Çölgeçen, Havva Atar, Belisa Kaleci, Tuğba Ekiz-Yılmaz
Recently, Mitrofanova L et al. explained that glioblastoma consists of different type of cells like pericytes, gliomas, astrocytomas, etc. Some of these cells that are CD117 positive, are also called telocytes (Tcs).41 These unique cells are located in the neighborhood of vessels and are responsible for maintenance of tumor growth and have stem cell like properties. In addition, Mou et al. published that Tcs had contributed to typical tumor formation and promoted the proliferation of tumoral cells along with the other stromal cells.42 And also, Mirancea et al. reported that Tcs seem to promote the tumor formation to become even more invasive.43 In our study, we lost a lot of cells due to the effect of the herb, but also found out that a part of the living cells which stained with immunocytochemistry highly expressed CD117. The presence of this large number of positive cells made us think that these cells that remained unaffected or slightly affected by the drug, might actually be Telocytes. And also, while Trifolium pratense L. is effective on many other cells that are forming the glioblastoma microenvironment, its activity on CD117 positive cells is seen to be limited. As it is known, CD117 is a tyrosine kinase receptor. As a result, tyrosine kinase inhibitors like imatinib are used for treatment of gastrointestinal tumors, Ewing sarcoma and ovarian cancers that are rich in CD117 positive cells.44 When we look from this aspect, we think that Trifolium pratense L. can be more effective when used together with tyrosine kinase inhibitors like imatinib.
Related Knowledge Centers
- Cluster of Differentiation
- Gametogenesis
- Haematopoiesis
- Protein Dimer
- Receptor Tyrosine Kinase
- Hematopoietic Stem Cell
- Melanocyte
- Cancer
- Lysosome
- Cluster of Differentiation
- Rtk Class III