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

Gastrointestinal stromal tumors (GISTs) represent a distinct and the most important subset of mesenchymal tumors of the GI tract. These tumors are both phenotypically and genotypically different from true leiomyomas and usually express CD34, a hematopoietic progenitor cell antigen. CD34, however, is also present in a wide variety of fibroblastic and endothelial cell tumors. In this immunohistochemical study of CD117, we evaluated 85 cases of GIST and more than 150 other mesenchymal tumors, including leiomyomas and schwannomas. CD117, the c-kit proto-oncogene product, is expressed in subsets of hematopoietic stem cells, mast cells, melanocytes, and interstitial cells of Cajal of the GI tract. CD117 was almost always (85%) expressed in both benign and malignant GISTs. CD117 was observed both in the spindle cell and epithelioid subtypes of GISTs in all locations. In addition to reacting with the CD34-positive GISTs, CD117 was positive in some CD34-negative cases. Approximately one-third of GISTs coexpressed CD117 and smooth muscle actins. In contrast, true leiomyomas (desmin and actin-positive) and schwannomas in both GI and peripheral locations were consistently negative for CD117. Solitary fibrous tumors and Kaposi's sarcomas, which are typically CD34 positive, were consistently CD117 negative. Among the CD34-positive tumors that showed occasional CD117 reactivity were dermatofibrosarcoma protuberans (1 of 7) and hemangiopericytoma (2 of 10). Other mesenchymal tumors that were variably CD 117 positive included clear cell sarcoma (7 of 15), metastatic melanoma (9 of 25), and malignant fibrous histiocytoma (1 of 20). These results indicate that CD117 is a specific marker for GIST among tumors that occur in the GI tract and adjacent regions. CD117 expression also separates GISTs from true leiomyomas and gastric schwannomas.
 ...
PMID:CD117: a sensitive marker for gastrointestinal stromal tumors that is more specific than CD34. 972 May

Gastrointestinal stromal tumour (GIST) is the designation used here to identify the most common subset of gastrointestinal mesenchymal tumours specific to those sites. These tumours have unique histological, immunophenotypic and molecular genetic features that set them apart from typical smooth muscle tumours and schwannomas; however, by tradition, they have been classified as GI-smooth muscle tumours, or stromal tumours/smooth muscle tumours. GISTs occur predominantly in persons over 40 years of age with an equal sex incidence. Benign GISTs outnumber the malignant ones by a margin of 10:1. GISTs occur throughout the gastrointestinal tract, but are most common in the stomach (60-70%) and small intestine (30%). GISTs are rare in esophagus, colon and rectum. Histologically they may show a spindle cell or epithelioid pattern (the former largely corresponds with the designation of cellular leiomyoma and the latter with that of leiomyoblastoma). Immunohistochemically most GISTs are positive for CD34 and c-kit protein (CD117); the latter is quite specific for GISTs among mesenchymal tumours. Genetically GISTs commonly show DNA losses in the long arm of chromosome 14, and c-kit gene mutations occur at least in some cases. c-kit is also expressed in the interstitial cells of Cajal, the gastrointestinal pacemaker cells, and relationship of GISTs to these cells has been proposed recently. GISTs differ histologically, immunohistochemically and genetically from typical (esophageal) leiomyomas that are negative for c-kit and CD34 and neither show DNA-losses in 14q nor c-kit mutations. Evaluation of malignancy of GISTs is based on mitotic count, tumour size and extra-gastrointestinal spread. Tumours with mitotic counts higher than 5/10 high power fields or larger than 10 cm have a significant risk for recurrence and metastasis and are considered histologically malignant; however, some tumours with mitotic activity < 1/10HPF may metastasize indicating some uncertainty in malignant potential of GISTs, especially those larger than 5 cm.
 ...
PMID:Gastrointestinal stromal tumours. 989 65

Gastrointestinal stromal tumors (GISTs) comprise the largest subset of mesenchymal tumors of the gastrointestinal tract. These neoplasms differ histologically and immunohistochemically from typical leiomyomas and leiomyosarcomas. Most GISTs express CD34 and CD117 (c-kit protein) but not desmin. Recently, gain-of-function mutations of c-kit proto-oncogene have been shown in five solitary GISTs and in tumors and leukocytes from a family with multiple GISTs. An in-frame deletion or a point mutation in exon 11 of c-kit was detected in these cases. Stable transfection of the mutant c-kit complementary DNA was also shown to induce malignant transformation of murine lymphoid cells, suggesting that the c-kit mutations contribute to tumor development. In this study, we evaluated 43 GISTs and 14 smooth muscle tumors for mutations in the exon 11 of c-kit by a PCR-assay. Half of the malignant GISTs (12/24) and only one benign GIST (1/19) revealed mutant bands. No mutant bands were found in 3 leiomyomas and 11 leiomyosarcomas. Sequence analysis confirmed the presence of an in-frame deletion of 3-21 bp in all 13 GISTs with mutant bands. Wild-type bands from 8 malignant and 11 benign GISTs and 7 smooth muscle tumors without mutant bands were cloned and sequenced. Additional mutations were found in 3 malignant and 2 benign GISTs. There were no mutations in 3 leiomyomas and 4 leiomyosarcomas. The mutation status of exon 11 did not correlate with immunohistochemically detectable expression of the CD117, as virtually all GISTs with or without such mutations showed CD117 immunoreactivity. The c-kit mutations occur preferentially in malignant GISTs and might be a clinically useful adjunct marker in the evaluation of GISTs. The conservation of the c-kit mutation pattern, observed in consecutive lesions from the same patients, suggests that these mutations might be useful tumor markers in monitoring recurrence or minimal residual disease.
 ...
PMID:Mutations in exon 11 of c-Kit occur preferentially in malignant versus benign gastrointestinal stromal tumors and do not occur in leiomyomas or leiomyosarcomas. 991 18

Identification of genetic alterations has contributed greatly to the understanding of sarcoma biology. Additionally, detection of these abnormalities is providing new tools for the diagnosis of sarcomas. In this paper, three important new genetic findings from the past year are reviewed, including the t(12;15) translocation of congenital fibrosarcoma, mutation of the putative tumor suppressor gene hSNF5/INI1 in malignant rhabdoid tumor, and the association of c-kit mutations with gastrointestinal stromal tumor. Highlighted are important studies concerning mechanisms of chromosomal translocation, functions of sarcoma-specific fusion proteins, genetic abnormalities other than translocations, molecular diagnosis, and molecular profiling of gene expression. Particular emphasis is placed on information obtained with comparative genomic hybridization and microarray techniques, because these powerful technologies will facilitate the rapid acquisition of data that provide insight into the molecular genetic and biologic basis of sarcomas.
 ...
PMID:Genetics and the biologic basis of sarcomas. 1041 79

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.
 ...
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 most common mesenchymal tumor of the gastrointestinal tract. Gain-of-function mutations in the juxtamembrane domain of the c-kit gene have been found in several GISTs. In this study, we examined the correlation between the presence of c-kit mutation and prognosis in 124 cases of GIST. DNA samples were extracted from paraffin sections. Exon 11 of the c-kit gene encoding the juxtamembrane domain and exon 17 encoding the kinase domain were amplified by PCR and sequenced. Most GISTs (89%) express the KIT protein, and missense mutations of exon 11 were found in 71 of 124 GISTs (57%). No mutations were detectable in exon 17. These 71 mutation-positive GISTs were larger in size and had more frequently invaded adjacent tissues than did the 53 mutation-negative GISTs. Histologically, the mutation-positive GISTs showed higher mitotic figures and more necrosis and hemorrhage. The patients with mutation-positive GISTs showed more frequent recurrences (P = 0.0005) and higher mortality (P = 0.0001) than did those with mutation-negative GISTs. The c-kit mutation was an independent prognostic factor for overall and cause-specific survival of the patients with GISTs. These results suggest that GISTs may be divided into mutation-positive and -negative subtypes. The prognosis was worse in patients with mutation-positive GISTs than in those with mutation-negative GISTs. Thus, mutation of the c-kit gene may be a good prognostic marker of GISTs.
 ...
PMID:Effect of c-kit mutation on prognosis of gastrointestinal stromal tumors. 1048 75

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.
 ...
PMID:Gastrointestinal stromal tumors: recent advances in understanding of their biology. 1053 70

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the GI tract, and expresses KIT and CD34 in most cases. Gain-of-function mutation of the c-kit proto-oncogene has been described, but its significance in GIST has not yet been fully evaluated. Mutation in exon 11 of the c-kit gene was determined by both polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing in primary and metastatic GISTs and esophageal leiomyomas in Japanese subjects. C-kit gene mutation was identified in 15 of 48 primary GISTs (31%), four of seven metastatic GISTs, but none of the leiomyomas. Three mutations were mis-sense point mutations, and 16 were in-frame deletions of 3-48 bp. C-kit gene mutation was observed equally in low- and high-risk groups, and was not related to any clinical and pathologic factors, phenotypes or Ki-67 labeling index (LI) of tumor cells. In five of 15 deletion mutations (four in primary tumors and one in a metastatic tumor), the mutations were present at the distal location of exon 11 of the c-kit gene, which was a minor mutation in previous reports from Finland and the USA. C-kit gene mutations in GIST are not always related to a poor prognosis, but further comparative studies are necessary in Western and Japanese populations.
 ...
PMID:C-kit gene abnormalities in gastrointestinal stromal tumors (tumors of interstitial cells of Cajal. 1066 49

Although rare elsewhere in the gastrointestinal tract, leiomyomas (LMs) are the most common esophageal mesenchymal neoplasms. In contrast, gastrointestinal stromal tumors (GISTs) predominate in the stomach and intestines but have not been documented in the esophagus. This study was undertaken to determine the clinicopathologic features and frequency of esophageal GISTs compared with LMs and leiomyosarcomas (LMSs) of the esophagus. A total of 68 stromal/smooth muscle tumors from the Armed Forces Institute of Pathology and the Haartman Institute of University of Helsinki were reclassified by current histologic and immunohistochemical criteria. There were 17 GISTs, 48 LMs, and three LMSs. The esophageal GISTs occurred in 12 men and five women with a median age of 63 years (range, 49-75 years). All tumors were from the lowest third of the esophagus, and the most common complaint was dysphagia, whereas two tumors were detected incidentally. Histologically the tumors had an overall basophilic appearance and showed combinations of solid, myxoid, and perivascular collarlike patterns with a spindle cell histology in 13 patients and epithelioid histology in four patients. All tumors were positive for CD117 and for CD34, whereas two patients were also positive for alpha-smooth muscle actin (SMA) and three patients were positive for desmin. One patient showed a unique immunophenotype with coexpression of CD117, CD34, SMA, and desmin. Nine patients died of disease, including all who had a tumor larger than 10 cm, and also one patient whose tumor showed five mitoses per 50 high-power fields. In comparison, esophageal LMs (n = 48) occurred in a younger population (median age, 35 years) but, similar to the GIST group, men predominated (67%). All LMs were clinically indolent tumors with no tumor-related mortality. The LMs showed eosinophilic cytoplasm, and were positive for desmin and SMA, and negative for CD117 and CD34. All three LMSs were large high-grade tumors that showed muscle cell markers but no CD117. All patients died of disease. Esophageal GISTs showed mutations in exon 11 of c-kit as described previously in gastric and intestinal GISTs. The separation of GISTs from esophageal LMs is important diagnostically because the former group has a high risk of malignant behavior.
 ...
PMID:Esophageal stromal tumors: a clinicopathologic, immunohistochemical, and molecular genetic study of 17 cases and comparison with esophageal leiomyomas and leiomyosarcomas. 1068 Aug 89

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.
 ...
PMID:A case of gastrointestinal stromal tumor of the stomach. 1081 97


1 2 3 4 5 6 7 8 9 10 Next >>