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)

The tumor suppressor p53 transcriptionally regulates a large number of target genes that may affect cell growth and cell death pathways. To better understand the role of p53 loss in tumorigenesis, we have developed a mouse mammary cancer model, the Wnt-1 TG/p53 model. Wnt-1 transgenic females that are p53-/- develop mammary adenocarcinomas that arise sooner, grow faster, appear more anaplastic, and have higher levels of chromosomal instability than their Wnt-1 transgenic p53+/+ counterparts. In this study, we used several assays to determine whether the presence or absence of p53 affects gene expression patterns in the mammary adenocarcinomas. Most of the differentially expressed genes are increased in p53+/+ tumors and many of these represent known target genes of p53 (p21WAF/C1P1, cyclin G1, alpha smooth muscle actin, and cytokeratin 19). Some of these genes (cytokeratin 19, alpha smooth muscle actin, and kappa casein) represent mammary gland differentiation markers which may contribute to the inhibited tumor progression and are consistent with the more differentiated histopathology observed in the p53+/+ tumors. Several differentially expressed genes are growth regulatory in function (p21, c-kit, and cyclin B1) and their altered expression levels correlate well with the differing growth properties of the p53+/+ and p53-/- tumors. Thus, while tumors can arise and progress in the presence of functioning wild type p53, p53 may directly or indirectly regulate expression of an array of genes that facilitate differentiation and inhibit proliferation, contributing to a more differentiated, slow growing, and genomically stable phenotype.
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PMID:Differential gene expression in mouse mammary adenocarcinomas in the presence and absence of wild type p53. 1114 50

Ten cecal tumors were identified during the postmortem examination of seven horse carcasses at slaughter (one horse had three tumors). The multinodular and hemorrhagic tumors ranged from 1 to 10 cm in diameter and consisted of spindle cells arranged in thin, interconnected trabeculae that were often separated by sinuses filled with mucinous fluid, erythrocytes, and siderophages. Spindle cells of all tumors were immunopositive for vimentin, neuron-specific enolase, and c-kit protein but lacked reactivity with antibodies to glial fibrillary acidic protein, S100 protein, and desmin. In one tumor, spindle cells diffusely bound antibodies to synaptophysin. Most tumors contained focal reactivity to smooth muscle actin antibodies; one tumor reacted diffusely. Ultrastructurally, tumor cells were connected by desmosome-like structures and exhibited extended cell processes; some contained dense core neurosecretory granules. These equine stromal tumors appeared to share some characteristics with human gastrointestinal stromal tumors.
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PMID:Gastrointestinal stromal tumors of the equine cecum. 1128 Mar 86

Occlusion of the anterior descending left coronary artery leads to ischemia, infarction, and loss of function in the left ventricle. We have studied the repair of infarcted myocardium in mice using highly enriched stem/progenitor cells from adult bone marrow. The left coronary artery was ligated and 5 hours later Lin- c-kit+ bone marrow cells obtained from transgenic male mice expressing enhanced green fluorescent protein (EGFP) were injected into the healthy myocardium adjacent to the site of the infarct. After 9 days the damaged hearts were examined for regenerating myocardium. A band of new myocardium was observed in 12 surviving mice. The developing myocytes were small and resembled fetal and neonatal myocytes. They were positive for EGFP, Y chromosome, and several myocyte-specific proteins including cardiac myosin, and the transcription factors GATA-4, MEF2, and Csx/Nkx2.5. The cells were also positive for connexin 43, a gap junction/intercalated disc component indicating the onset of intercellular communication. Myocyte proliferation was demonstrated by incorporation of BrdU into the DNA of dividing cells and by the presence of the cell cycle-associated protein K167 in their nuclei. Neo-vascularization was also observed in regenerating myocardium. Endothelial and smooth muscle cells in developing capillaries and small arterioles were EGFP-positive. These cells were positive for Factor VIII and alpha smooth muscle actin, respectively. No myocardial regeneration was observed in damaged hearts transplanted with Lin- c-kit- bone marrow cells, which lack bone marrow-regenerating activity. Functional competence of the repaired left ventricle was improved for several hemodynamic parameters. These in vivo findings demonstrate the capacity of highly enriched Lin- c-kit+ adult bone marrow cells to acutely regenerate functional myocardium within an infarcted region.
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PMID:Transplanted adult bone marrow cells repair myocardial infarcts in mice. 1145 11

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

The purpose of this work was to study the expression in gastrointestinal stromal tumors (GISTs) of various antigens, including the protein tau associated with enteric neuronal differentiation; to compare their expression with that of c-kit, known to be associated with interstitial cell of Cajal differentiation; and to correlate their expression with the observation of ultrastructural features of gastrointestinal autonomic nerve tumors. Twenty-six GISTs of the stomach and 16 GISTs of the small bowel were included in the study group. Thirty-five tumors served as controls. Tissue sections were immunostained with vimentin, CD34, desmin, specific smooth muscle actin, S100 protein, neuron-specific enolase, PGP9.5, neurofilament, bcl-2 oncoprotein, synaptophysin, chromogranin A, c-kit, and tau. Twenty-one of these tumors were also analyzed ultrastructurally. Of the 42 GISTs, 28 were predominantly spindled, 7 were predominantly epithelioid, and 7 were a mixture of epithelioid and spindle cells. Ten primary GISTs were classified as benign, 9 as borderline, and 23 as malignant. Metastatic dissemination was present at primary surgery in 1 case and eventually developed in 6 patients. Six disease-related deaths were counted. In normal submucous and myenteric plexuses of stomach and small bowel, ganglion cell bodies and nerve fibers strongly expressed tau. Twenty (76.9%) GISTs of the stomach and 12 (75%) of the small bowel expressed tau. Tau often showed intense, diffuse staining patterns in both spindled and epithelioid tumors. Ten (100%) of the 10 benign GISTs, 7 (77.8%) of the borderline GISTs, and 15 (65.2%) of the 23 frankly malignant GISTs expressed tau. Thirty-six GISTs expressed at least 2 different neuronal markers. A coexpression of the neuronal markers and c-kit was observed in 90% of GISTs. The expression of tau was observed in 12 of the 15 GISTs with dense core granules, considered as the definitive finding for a diagnosis of gastrointestinal autonomic nerve tumors. Ten of these also expressed c-kit; 9 were malignant. Tau also immunostained other intra-abdominal tumors, including neuroendocrine carcinomas, paragangliomas and desmoplastic round cell tumors. This immunohistochemical study shows that GISTs are specific tumors of the digestive tract and are nearly always characterized by simultaneous neuronal and interstitial cell of Cajal differentiation. Although the loss of tau expression is observed only in borderline and malignant tumors, its prognostic value is not clear cut.
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PMID:Expression of microtubule-associated protein tau by gastrointestinal stromal tumors. 1172 54

Malignant mesenchymal tumors of the gallbladder are exceedingly rare. We report a malignant stromal tumor of the gallbladder with a phenotype of interstitial cells of Cajal. To our knowledge, only the benign counterpart of this tumor has been described previously. A 34-year-old woman presented with right upper quadrant abdominal pain. At the time of cholecystectomy, the gallbladder was noted to have a thickened wall and a polypoid mass arising in the neck of the gallbladder. Histologic sections showed a cellular proliferation of spindle neoplastic cells that were arranged in short fascicles. Numerous mitotic figures and foci of necrosis were noted. The neoplastic cells expressed CD117 (c-Kit protein) and vimentin. They were negative for smooth muscle actin, desmin, myoglobin, cytokeratin, S100 protein, and CD34. Our case demonstrates that a malignant stromal tumor that is histologically and immunohistochemically identical to gastrointestinal stromal tumor can occur in the gallbladder, and that the expression of CD117 may be of therapeutic importance.
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PMID:Malignant stromal tumor of the gallbladder with interstitial cells of Cajal phenotype. 1190 May 79

Primary malignant tumors of the small intestine are rare. Malignant gastrointestinal stromal tumors are the third most common neoplasm among primary malignant small bowel tumors. A 56-year-old woman was admitted to our hospital because of appetite loss and dyspnea with movement. On admission, physical examination revealed severe anemia in her conjunctiva and a tumor in her left abdomen. Her hemoglobin level was 6.2 g/dL and other laboratory data were normal. Abdominal ultrasonograms and computed tomograms revealed a 55 x 70-mm heterogeneous mass and multiple low-density masses in the liver. Superior mesenteric arteriograms revealed a hypervascular tumor fed by the jejunal arteries. A malignant gastrointestinal stromal tumor arising from the jejunum with liver metastases was suspected. Partial resection of the affected jejunum and left trisegmentectomy of the liver were performed. The resected primary tumor was 120 x 45 x 65 mm. The tumor was mainly submucosal, but extended outside the jejunum; it was elastically firm and multiloculated. A small ulcer was seen on the mucosal side. The metastatic liver tumors were solid or cystic with diameters of 20 to 40 mm. Histopathological examination revealed that the tumors were characterized by fascicular proliferation of spindle-shaped cells. Immunohistochemical staining was positive for CD34 and c-kit, and negative for S-100 protein and smooth muscle actin. This case was a malignant gastrointestinal stromal tumor originating in the jejunum with liver metastases. The primary tumor and liver metastases were successfully resected simultaneously.
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PMID:Malignant gastrointestinal stromal tumor of the jejunum with liver metastasis. 1223 33

Although separating gastrointestinal stromal tumor (GIST) from mesenteric fibromatosis and sclerosing mesenteritis is clinically important, this distinction sometimes poses problems for practicing pathologists. In the STI571 (Gleevec, Imatinib) era, the problem may be further compounded when protocol-driven staining for CD117 (c-kit) is performed on spindle cell proliferations presenting in the bowel wall and mesentery using an antibody known to react with the majority of mesenteric fibromatoses when other antibodies are more specific. Because most mesenteric fibromatoses have mutations in the pathway and hence have abnormal nuclear accumulation of beta-catenin protein, we studied beta-catenin expression among a panel of other immunohistochemical stains to distinguish mesenteric fibromatosis, GIST, and sclerosing mesenteritis. Examples of gastrointestinal stromal tumors (GIST, 11), sclerosing mesenteritis (5), and mesenteric fibromatosis (10) were retrieved from the archives of our institutions. Cases were studied with an immunohistochemical panel consisting of CD117, beta-catenin, CD34, smooth muscle actin, desmin, keratin, and S-100 protein. Cases were scored as "negative," "focally positive," or "diffusely positive." In evaluating beta-catenin, nuclear accumulation was required. GIST all had CD117 (11 of 11, diffuse) and CD34 (11 of 11, diffuse) with variable actin (5 of 11, focal) and negative desmin, keratin, S-100 protein. All GIST lacked beta-catenin (0 of 11). Mesenteric fibromatosis had CD117 (6 of 10, 3 focal, 3 diffuse), typically expressed more weakly than in GIST, actin (5 of 9, focal), and desmin (3 of 8, focal) in keeping with myofibroblastic differentiation but lacked CD34, S-100, and keratin. CD117 staining was not eliminated by use of a non-avidin-biotin technique. Nuclear beta-catenin was detected in 9 of 10 fibromatoses, including one case associated with familial adenomatous polyposis. Two of five sclerosing mesenteritis cases focally expressed CD117. None of the sclerosing mesenteritis cases had nuclear beta-catenin. Sclerosing mesenteritis cases were otherwise fibroblastic and myofibroblastic with focal actin in 5 of 5 and negative desmin, keratin, and S-100 protein but one had CD34 (1 of 5, focal). With increasing protocol-driven interest in evaluating bowel wall and mesenteric spindle cell lesions using CD117 (c-kit) antibodies, it is important for practicing pathologists to be aware that lesions other than GISTs are likely to express this antigen using certain antibodies. beta-Catenin staining identifies lesions that are, instead, mesenteric fibromatoses.
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PMID:Beta-catenin immunohistochemistry separates mesenteric fibromatosis from gastrointestinal stromal tumor and sclerosing mesenteritis. 1236 44

Endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNA) is considered to be a reliable and accurate method for the evaluation of submucosal lesions in the gastrointestinal tract. Herein, we report our experience with the diagnosis of 10 cases of gastrointestinal stromal tumor (GIST) using EUS-FNA. The materials obtained from the EUS-FNA were stained with the rapid Romanowsky or the Papanicolaou method for cytologic examination. The subsequent surgical resection specimens were submitted for histopathologic examination. Immunoperoxidase stains were performed on the cell blocks and/or representative histologic sections of the tumor using commercially available antibodies against c-kit (CD117), CD34, S-100, and smooth muscle actin. Of the 10 cases studied, there were five men and five women with an average age of 62 years (range, 38 to 87 years). Five tumors were located in the stomach, and five in the duodenum. Tumor size ranged from 3.5 to 16.2 cm. Immediate on-site evaluation and cytologic diagnoses were given in eight cases (80%) with an average of three passes. The diagnoses were confirmed by strong and diffuse tumor cell c-kit immunoreactivity in the cell blocks. However, the final diagnoses of two other cases (20%) were not established until surgical resections were obtained. Retrospectively, reviews of cytologic smears of both cases demonstrated rare cohesive sheets or clusters of spindle cells with cigar-shaped nuclei. These observations were initially misinterpreted as benign fibrous tissue and/or fragments of smooth muscle of the gastrointestinal wall such as one might encounter in a routine transgastric or transduodenal EUS-FNA. The current study showed that when combining cytologic and immunocytochemical studies, EUS-FNA is accurate and efficient in the diagnosis of GIST. It exemplified the importance of considering GIST in the differential diagnosis of gastrointestinal lesions and also demonstrated the potential pitfalls of EUS-FNA evaluation of submucosal lesions in the gastrointestinal tract.
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PMID:Diagnosis of gastrointestinal stromal tumor by endoscopic ultrasound-guided fine needle aspiration biopsy--a potential pitfall. 1237 22

We analyzed the clinicopathological features of 12 gastrointestinal (GI) schwannomas and compared them with those of 37 GI stromal tumors (GISTs) and 15 leiomyomas. Grossly, the schwannomas showed rubbery to firm, yellow-white to tan, glistening, and often trabeculated cut surfaces, resembling soft tissue schwannomas. The GISTs were firm to soft or fish-flesh tan, gray-pink, or variegated tumors with a degenerative change, and the leimyomas resembled typical uterine leiomyomas. Histologically, GI schwannomas were moderately cellular tumors with focal significant nuclear pleomorphism and rare mitotic figures. A characteristic peripheral lymphoid cuff was observed in all cases, but was indistinct in two cases. The GISTs were highly cellular spindle cell, epithelioid or, occasionally, pleomorphic tumors with basophilic appearance. Leiomyomas were paucicellular tumors with eosinophilic appearance. Immunohistochemically, schwannomas were S-100 protein- and glial fibrillary acidic protein (GFAP)-positive, but were negative for c-kit, CD34, and smooth muscle actin (SMA). GISTs were all c-kit- and/or CD34-positive, but GFAP-negative. Leiomyomas were SMA-positive and were negative for c-kit, CD34, S-100 protein, and GFAP. The mean Ki-67 index of schwannoma was 0.7, and those of GIST and leiomyoma were 5.9 and 0.3, respectively. The patients with schwannomas and leiomyomas had a favorable outcome, whereas 12 patients with GISTs showed progression and died of disease. The separation of GISTs from schwannomas is clinically important because the former group has a high risk of malignant behavior. GI schwannomas differed from the conventional soft tissue schwannomas in that they had peripheral lymphoid cuffs, lacked fibrous capsule and vascular hyalinization, and rarely showed degenerative changes. GI schwannomas, however, resembled soft tissue schwannomas in many aspects, and the clinical, gross, histological, and immunohistochemical features were different from those of GISTs and leiomyomas.
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PMID:Schwannomas of the gastrointestinal tract: clinicopathological features of 12 cases including a case of esophageal tumor compared with those of gastrointestinal stromal tumors and leiomyomas of the gastrointestinal tract. 1244 Jul 83


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