Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastrointestinal stromal tumor or smooth muscle tumor (GIST) is the designation for a major subset of gastrointestinal mesenchymal tumors that histologically, immunohistochemically, and genetically differ from typical leiomyomas, leiomyosarcomas, and schwannomas. Because GISTs, like the interstitial cells of Cajal, the gastrointestinal pacemaker cells, express CD117 (c-kit protein), the origin of GISTs from the interstitial cells of Cajal has been recently proposed. Comparison of GISTs primary in the omentum and mesentery to GISTs primary in the tubular gastrointestinal tract is of particular diagnostic and histogenetic interest in view of the possible similarity of these tumors with the GIST group. In this study, we analyzed 14 omental and 12 mesenteric primary mesenchymal tumors representing smooth muscle tumors or GISTs. These tumors were phenotypically compared with gastric and small intestinal GISTs, leiomyomas of the esophagus, and leiomyosarcomas of the retroperitoneum. Most (13 of 14) omental and mesenteric (10 of 12) tumors showed histologic features similar to GISTs with elongated spindle cells or epithelioid cells with high cellularity; most of these tumors showed low mitotic activity. Omental and mesenteric GISTs were typically positive for CD117 and less consistently for CD34. They often showed alpha-smooth muscle actin reactivity but were virtually negative for desmin and S-100 protein. One omental and two mesenteric tumors showed features of leiomyosarcoma with ovoid, less elongated nuclei, cytoplasmic eosinophilia; all these tumors had significant mitotic activity. These tumors were positive for alpha-smooth muscle actin and two of them for desmin, but all were negative for CD34 and CD117, similar to retroperitoneal leiomyosarcomas. Tumor-related mortality occurred in the group of mesenteric GISTs, but not in the group of omental GISTs. In contrast, all three patients with a true leiomyosarcoma of the omentum or mesentery had documented liver metastases or died of tumor. In summary, we show that tumors phenotypically identical with GISTs occur as primary tumors in the omentum and mesentery. The occurrence of CD117-positive tumors outside the gastrointestinal tract militates against an origin of these tumors exclusively from the interstitial cells of Cajal.
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PMID:Gastrointestinal stromal tumors/smooth muscle tumors (GISTs) primary in the omentum and mesentery: clinicopathologic and immunohistochemical study of 26 cases. 1047 72

Gastrointestinal stromal tumor (GIST) is the preferred term for mesenchymal tumors specific for the gastrointestinal tract (60% in stomach, 30% small intestine, 10% elsewhere). GISTs include most tumors previously designated as leiomyoma, cellular leiomyoma, leiomyoblastoma, and leiomyosarcoma. However, in the esophagus, leiomyoma is the most common mesenchymal tumor. GISTs are composed of spindle (70%) or epithelioid (30%) cells, and 10%-30% are malignant showing intra-abdominal spread or liver metastases. They are immunohistochemically positive for c-kit (CD117), CD34, and sometimes for actin but are almost always negative for desmin and S100-protein. The malignant GISTs especially show activating mutations in the c-kit gene. GISTs and gastrointestinal autonomic nerve tumors (GANT) overlap. The cell of origin is not fully understood, but resemblance to the interstitial cells of Cajal, expression of some smooth muscle markers, and occurrence outside of the GI-tract suggest origin from multipotential cells that can differentiate into Cajal and smooth muscle cells.
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PMID:Gastrointestinal stromal tumors: recent advances in understanding of their biology. 1053 70

In a 55-year-old man, a tumor about 3 cm in diameter was detected in the upper abdomen by abdominal ultrasound screening during follow-up of chronic hepatitis C discovered in 1990. There were no symptoms and no abnormalities on physical examination. Tests for tumor markers were negative. By barium meal and gastroscopy, submucosal tumor was found on the lesser curvature of the stomach, with bridging fold in the absence of central ulceration. Biopsy revealed no tumor tissue. Under the diagnosis of submucosal tumor of the stomach, either a leiomyoma or leiomyosarcoma, partial resection of stomach was performed. Direct invasion of the surrounding organs, lymph node metastasis or distant metastasis was not observed grossly in the operation. Histologic examination of the resected specimen revealed proliferation of spindle cells and oval cells in an interlacing pattern. Immunohistochemistry for CD34, vimentin and c-kit protein was strongly positive, while smooth muscle actin, S-100 protein, desmin and p53 protein were negative. The proliferating cell nuclear antigen index was about 50%, while the MIB-1 index was < or = 1%. From these findings, this tumor was diagnosed as a gastrointestinal stromal tumor of the uncommitted type.
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PMID:A case of gastrointestinal stromal tumor of the stomach. 1081 97

Gastrointestinal stromal tumors (GISTs), the specific KIT-positive mesenchymal tumors of the gastrointestinal tract, have been sporadically reported in the rectum, but there are few clinicopathologic series. In this study we analyzed the clinicopathologic features of 133 anorectal GISTs, 3 intramural leiomyomas (LMs), and 8 leiomyosarcomas (LMSs) from the files of the Armed Forces Institute of Pathology and the Haartman Institute of the University of Helsinki. Ninety-six GISTs were documented as KIT-positive and three additional ones as CD34-positive. Thirty-four tumors were included by their histologic similarity to KIT- or CD34-positive cases. GIST-specific c-kit gene mutations, mostly in exon 11, were documented in 18 of 29 cases (62%). The GISTs occurred in adults with the age range of 17-90 years (median 60 years) with a significant male predominance (71%). The tumors ranged from small asymptomatic intramural nodules to large masses that bulged into pelvis causing pain, rectal bleeding, or obstruction. They were mostly highly cellular spindle cell tumors; four tumors had an epithelioid morphology. The tumors coexpressed CD34 and KIT and were rarely positive for smooth muscle actin or desmin and never for S-100 protein. Seventy percent of patients with tumors >5 cm with more than 5 mitoses/50 high power fields (HPF) (n = 31) died of disease, whereas only one tumor <2 cm with <5 mitoses/50 HPF (n = 21) recurred and none caused death. Long latency was common between primary operation and recurrences and metastases; either one occurred in 60 of 111 patients with follow-up (54%). Distant metastases were in the liver, bones, and lungs. Three benign actin- and desmin-positive and KIT-negative intramural LMs, similar to those seen in the esophagus, were identified. There were eight LMSs, six of which formed a polypoid intraluminal mass and were actin-positive and KIT-negative. Despite high mitotic counts, only one LMS patient died of disease. A great majority of rectal smooth muscle and stromal tumors are GISTs, which have a spectrum from minimal indolent tumors to overt sarcomas. Intramural LMs are exceptional, and true LMSs are rare, and similar to colonic ones, often present as intraluminal polypoid masses that appear to have a better prognosis than GISTs with similar mitotic rates.
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PMID:Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas in the rectum and anus: a clinicopathologic, immunohistochemical, and molecular genetic study of 144 cases. 1168 71

42 gastrointestinal mesenchymal tumors are analyzed by the authors with characterization of immunohistochemistry and DNA study. Out of 42 tumors, 29 GIST 3 leiomyoma, 4 leiomyosarcoma, 3 benign schwannoma, 1 soliter fibrous tumor, 1 inflammatory myofibroblastic tumor and 1 benign haemangiopericytoma were found. All 29 GIST but two could be characterized by c-kit (CD-117) and CD-34 positivity independently weather they displayed focal neurogenic and/or myogenic immunomarkers. In GIST group, 10 cases were benign, 6 borderline and 13 malignant. All benign cases were euploid by DNA study, the malignant tumours were highly aneuploid. Concerning the borderline GIST group by morphology, the aneuploid DNA content may speak for malignant biological behavior, and the diploid DNA content in low grade malignant GIST by morphology may speak for better outcome in the malignant group. There is a discussion about the nomenclature of this morphological group, about the role of the c-kit gene and the necessity of the immunohistochemistry and DNA content determination.
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PMID:[Gastrointestinal stromal tumors. Observations on the basis of 29 cases]. 1177 55

The nonepithelial, nonlymphoid tumors of the gastrointestinal tract are heterogeneous in terms of clinical presentation, behavior, pathology, and genetic features. Concepts regarding these tumors have changed rapidly over the past decade as nomenclature has evolved. Many of these tumors have no muscle differentiation, and designations such as leiomyoma or leiomyosarcoma are inappropriate for many of these neoplasms. With an improved understanding of the biology of these tumors, gastrointestinal stromal tumor (GIST) is used as a specific term for tumors of the gastrointestinal tract that lack markers of myogenic differentiation, but stain positive for vimentin, and express CD34 and CD117, the product of the c-kit oncogene. Both benign and malignant types are recognized. In addition to myogenic tumors and GIST, gastrointestinal autonomic nerve tumors (GANT) are also recognized. Complete en bloc surgical resection, when possible, is the cornerstone of therapy. Metastasis tends to occur to the liver and within the peritoneal cavity, especially in patients whose tumors have ruptured spontaneously or been violated by the surgeon. Incomplete surgical resection and metastatic disease indicate a dismal prognosis in the majority of patients. Recurrent or metastatic disease is often resected, but this has an uncertain impact on outcome. Operation may palliate patients with intestinal obstruction or other symptoms. For patients with unresectable disease, the results with systemic chemotherapy have been dismal. Treatment with doxorubicin/ifosfamide combinations is of dubious value. Hepatic arterial embolization, with and without intra-arterial chemotherapy, results in regression of liver metastases in selected patients. Regression has also been seen using intrahepatic arterial infusion of doxorubicin without embolization. The impact of such treatment on outcome, however, is poorly studied. Aggressive surgical resection of peritoneal metastases with intraperitoneal chemotherapy has been advocated, but requires formal study in large trials.
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PMID:Gastrointestinal stromal tumors. 1205 70

We have recently observed that many of our sarcoma patients presented also with thyroid disorders. Literature data are almost unavailable on this topic. The relationship between the sarcoma and thyroid disorders is examined. Retrospective analysis of files of patients with sarcoma and clinically overt thyroid disorders was carried out. Of the 375 patients with soft tissue sarcomas (STS) and 235 with bone sarcoma (BS) including small blue round cell tumors (SBRC), 28 patients (4.6%) had an associated significant thyroid disorder. The types of sarcoma were mainly liposarcoma followed by malignant fibrous histiocytoma, leiomyosarcoma and bone sarcoma. The primary sites were mainly limb and trunk. The interval between the diagnosis of the thyroid disorder and the sarcoma varied between -14 years (thyroid first) and +16.5 years (thyroid later) with a median of -0.2 years. Thyroid disorders included goiter, thyroiditis and carcinoma. There are both basic-science and clinical evidence to a possible common pathway that leads to the association between overt thyroid disorders and sarcomas of bone or soft tissues. Oncogene erbA activity is related to thyroid receptors to T3 and to development of sarcoma. Cross talk of the sarcoma oncogene and the erbA might contribute to the development of sarcoma. The thyroid hormone receptor and the highly related viral oncoprotein v-erbA are found exclusively in the nucleus as stable constituents of chromatin. It has been shown that v-erbA can block the spontaneous differentiation in erythroid cells transformed by various retroviral oncogenes. V-erbA can alter the spectrum of neoplasia induced by the v-src oncogene, which causes predominantly sarcomas and erythroblastosis in chicks. The erbA can cooperate with other oncogenes such as v-erbB or with v-fms, v-ras, and c-kit. Cooperation with v-myc may play a role in the development of rhabdomyosarcoma especially in thyroid hormone deficiency state. The possible clinical implications are the need to screen patients with sarcoma to thyroid disorders, and patients with thyroid disorders for malignant diseases.
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PMID:Sarcoma and thyroid disorders: a common etiology? 1206 23

Gastrointestinal stromal tumors (GISTs) are non differentiated sarcoma of the gastrointestinal tract and have for a long time been confused with well differentiated tumors and classified as leiomyosarcoma. These tumors are characterized immunohistochemically by CD 117 staining. This marker represents the expression of c-kit which is a receptor for growth factor with enzymatic activity (tyrosine kinase). Recent studies have found that an inhibitor of specific tyrosine kinase is effective in the treatment of GIST with an estimated response rate of more than 60%. This new drug could significantly improve the prognosis of these aggressive chemoresistant tumors.
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PMID:[At last, an effective therapy for non-differentiated GI sarcomas (gastro intestinal stromal tumor)]. 1241 Jan 26

The purpose of this study was to determine whether 3 tyrosine kinases known to be inhibited by imatinib mesylate are expressed in a variety of uterine sarcomas. The authors assessed c-kit, abl, and platelet-derived growth factor receptor-beta (PDGFR-beta) expression in 8 endometrial stromal sarcomas (ESSs), 5 leiomyosarcomas (LMSs), 4 high-grade endometrial sarcomas (HGESs), and 21 malignant mixed mullerian tumors (MMMTs). Tissue sections were stained with commercially available antibodies for c-kit, abl, and PDGFR-beta. Staining intensity was described as 0 (no staining), +1 (weak), +2 (moderate), and +3 (strong). Positive staining was defined as moderate to strong if found in more than 10% of tumor cells. Expression of c-kit ranged from 0% in LMSs to 25% in HGESs. Protein expression of abl was more significant, ranging from 25% in LMSs and ESSs to 43% in MMMTs. Only 1 LMS sample stained focally for abl (+1). Abl expression was observed in only the carcinomatous elements of the MMMTs, with diffuse staining in the cytoplasm and nucleus. In most, the staining intensity was +2. All tumors stained positive for PDGFR-beta. MMMT samples showed PDGFR-beta expression in both the carcinomatous and sarcomatous portions. In all samples, staining for PDGFR-beta was concentrated at the cell membrane and diffusely in the cytoplasm. These results indicate that many uterine sarcomas express 1 or more of the kinases targeted by imatinib mesylate and that further investigation of imatinib as a therapy for uterine sarcomas is warranted.
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PMID:Imatinib mesylate (gleevec)--targeted kinases are expressed in uterine sarcomas. 1589 30

Five cases of gastrointestinal stromal tumor metastatic to the ovary are reported. The average patient age was 59 years (range, 44-81 years). The primary tumor was in the small bowel or its mesentery (4 cases) or stomach (1 case). The primary and metastatic tumors were discovered synchronously in 3 cases. In the other 2 cases, the ovarian tumors were discovered 18 months before a gastric tumor was identified and 27 years after a small bowel tumor had been resected. The ovarian tumors (three of which were bilateral) were usually solid, tan, and lobulated. Microscopically, three tumors had a pure spindle cell morphology, and two both spindle and epithelioid cell components. The diagnosis in all 5 cases was confirmed with positive c-kit (CD117) and negative desmin immunostaining. Variably positive immunoreactivity for either or both h-caldesmon and smooth muscle actin was seen in all 5 cases, and 3 cases were CD34-positive. Four patients died between 1 and 6.5 years (mean, 2.8 years) from the time of ovarian tumor diagnosis. The main differential diagnostic consideration was leiomyosarcoma; the most important features to help exclude this diagnosis were an absence of tumor in the uterus, low histologic grade, and a desmin-negative, c-kit-positive immunophenotype. Other differential considerations, including endometrial stromal sarcoma and fibrosarcoma, are discussed. Most of the ovarian tumors in this series were initially diagnosed as tumors of other types, a misdiagnosis with significant therapeutic and prognostic implications because of the specific therapy now available for gastrointestinal stromal tumors.
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PMID:Gastrointestinal stromal tumors metastatic to the ovary: a report of five cases. 1595 57


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