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)

Currently, the immunohistochemical evaluation of smooth muscle differentiation is usually based on desmin, which also reacts with skeletal muscle and is not present in all smooth muscle tumors, and alpha-smooth muscle actin, which reacts with myoepithelial cells. Neither marker typically reacts with gastrointestinal stromal tumors (GISTs), previously classified as smooth muscle tumors or presently often classified as smooth muscle/stromal tumors. Two cytoskeleton-associated actin-binding proteins, calponin (CALP) and h-caldesmon (HCD), are putative smooth muscle markers that also react with myoepithelia. These markers are of particular interest in the immunohistochemical analysis of tumors; neither of them has been extensively documented in soft tissue tumors. In this study, we evaluated selected normal and reactive tissues and more than 250 mesenchymal tumors for CALP and HCD. Both markers were expressed in parenchymal and vascular smooth muscle cells in various organs and in myoepithelial cells. CALP also reacted with myofibroblasts of desmoplastic stroma. All of our 25 benign smooth muscle tumors from various locations were positive for CALP and HCD, as were most of the retroperitoneal and uterine leiomyosarcomas. HCD was more specific, because CALP also reacted with myofibroblastic lesions. The common reactivity of malignant fibrous histiocytomas with CALP and HCD suggests a combination of myofibroblastic and smooth muscle differentiation in these tumors. The GISTs (c-kit positive, usually actin negative) showed nearly consistent HCD reactivity, suggesting traits of smooth muscle differentiation. GISTs were usually CALP negative and showed a CALP expression pattern similar to that of alpha-smooth muscle actin. Although nonmuscle, nonmyofibroblastic tumors were negative for CALP and HCD, synovial sarcomas showed streaks of CALP-positive cells of unknown significance. CALP and HCD should be explored as markers to identify myofibroblastic and smooth muscle cell differentiation in mesenchymal tumors.
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PMID:Calponin and h-caldesmon in soft tissue tumors: consistent h-caldesmon immunoreactivity in gastrointestinal stromal tumors indicates traits of smooth muscle differentiation. 1046 76

Immunohistochemical and clinicopathological features of 58 gastrointestinal stromal tumors (GIST) were studied. One occurred in the esophagus, 41 in the stomach, nine in the small intestine, and seven in the large intestine. By using indirect immunoperoxidase staining for Cajal cell markers (c-kit protein and CD34), smooth muscle markers (alpha-smooth muscle actin, desmin, heavy caldesmon and calponin) and Schwann cell markers (S-100 protein and Leu 7), GIST were classified into five groups, such as Cajal cell type (n = 9), myogenic type (n = 5), Schwann cell type (n = 2), mixed cell type (n = 40) and undifferentiated type (n = 2). c-kit Protein (42/58; 72%) and CD34 (45/58; 78%) were commonly and diffusely expressed in GIST. Novel smooth muscle markers, caldesmon (29/58; 50%) and calponin (18/58; 31%), were useful in detecting myogenic characters of GIST. S-100 protein was expressed in 16 (28%) tumors, two of which were also reactive with Leu 7 (CD57). Three small bowel tumors with skeinoid fibers expressed the Cajal cell markers, and were categorizable in GIST. Clinicopathological analyses using aggressive (n = 21) and non-aggressive (n = 21) GIST indicated that the malignant potential was correlated with the intestinal location, large tumor size, high cellularity, necrosis, solid (non-interlacing bundled) pattern of growth, negativity of c-kit protein and/or CD34, high mitotic count, and high MIB-1 labeling.
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PMID:An immunohistochemical and clinicopathological study of gastrointestinal stromal tumors. 1050 50

Glomus tumors usually occur in the peripheral soft tissues, but similar tumors have also been reported in the stomach and occasionally in the intestines. However, the relationship of these tumors to peripheral glomus tumors and gastrointestinal stromal tumors has not been fully clarified because previous series of gastrointestinal glomus tumors predate availability of immunohistochemistry. This clinicopathologic study examined 32 gastrointestinal glomus tumors. All but one of the tumors were located in the stomach and the remaining tumor was from the cecum. The tumors occurred with a strong female predominance (23 females and 9 males) and a median age of 55 years (range 19-90 years). The gastric tumors typically presented with gastrointestinal bleeding or ulcer-like symptoms, and 14 tumors had mucosal ulceration. Five tumors were incidental findings. The tumor sizes varied from 1.1 to 7 cm (median 2 cm), and most were located in the antrum. Histologically, the tumors typically had a solid pattern of sharply demarcated, round glomus cells with prominent, mildly dilated pericytoma-like vessels. Vascular invasion and focal atypia were relatively common (seen in 11 and 13 cases, respectively), and low mitotic activity (1-4 per 50 high power fields), was seen in 10 cases. Immunohistochemically, all tumors were positive for alpha-smooth muscle actin and calponin, and nearly all had a net-like pericellular laminin and collagen type IV positivity. All tumors were negative for desmin and S-100 protein. Three tumors had focal synaptophysin positivity, but none was positive for chromogranin. All tumors lacked KIT expression and the GIST-specific mutations in the c-kit gene. Follow-up revealed one patient death of metastatic disease to liver at 50 months; this tumor had 1 mitosis per 50 high power fields, but had spindle cell foci, mild atypia, and vascular invasion. Thirteen patients were well and alive after long-term follow-up. Gastrointestinal glomus tumors occur almost exclusively in the stomach, and they have a good overall prognosis, but a small, unpredictable potential for malignant behavior exists. These tumors are phenotypically similar to peripheral glomus tumors and differ from epithelioid GISTs.
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PMID:Gastrointestinal glomus tumors: a clinicopathologic, immunohistochemical, and molecular genetic study of 32 cases. 1185 1

The expression of desmin, h-caldesmon, calponin, CD10, CD34, CD99, inhibin, and keratin (AE1/3-Cam 5.2) was studied in 10 conventional leiomyomas, 9 highly cellular leiomyomas, 9 epithelioid smooth muscle tumors, 9 leiomyosarcomas, 10 endometrial stromal tumors (4 with smooth muscle metaplasia), and 7 uterine tumors resembling ovarian sex cord tumors (UTROSCTs). c-kit expression was tested in 10 endometrial stromal tumors, 7 UTROSCTs, and 9 leiomyosarcomas. Desmin was positive in almost all smooth muscle tumors except those of epithelioid type, which were positive in only about half of the cases. It also stained areas of smooth muscle differentiation in endometrial stromal tumors and five of seven UTROSCTs. h-caldesmon was positive in almost all nonepithelioid smooth muscle tumors and in areas of smooth muscle differentiation in endometrial stromal tumors; it was positive in only about half of the epithelioid smooth muscle tumors and negative in all UTROSCTs. Calponin was positive in most tumor types. CD10 was positive in nine of 10 endometrial stromal tumors and five of seven UTROSCTs, although very focally in the latter group. It was also expressed, however, in almost all leiomyosarcomas, almost 50% of highly cellular leiomyomas, and rarely in the other smooth muscle tumors. CD34 was negative in the tested tumors with rare exceptions. CD99 and inhibin were positive in four of seven and one of seven UTROSCTs. Keratin positivity was found in most (five of seven) UTROSCTs and occasionally in smooth muscle tumors (seven of 37). c-kit was negative in all endometrial stromal tumors, UTROSCTs, and leiomyosarcomas. The major conclusions of this study are as follows: 1) Pure endometrial stromal tumors are usually desmin negative. 2) In contrast to some previous studies, CD10 expression was often seen in smooth muscle tumors, including most leiomyosarcomas and almost half of highly cellular leiomyomas. As a result, a panel of CD10, h-caldesmon, and desmin should be used and will distinguish endometrial stromal tumors from highly cellular leiomyomas in most cases. 3) In contrast to a previous study, no significant differences in immunoreactivity were seen between h-caldesmon and desmin in tumors with smooth muscle differentiation. 4) The absence of h-caldesmon in UTROSCTs helps separate them from epithelioid smooth muscle tumors. 5) UTROSCTs may express epithelial, stromal, and smooth muscle markers, suggesting divergent differentiation. 6) Our study shows less frequent inhibin expression in the sex cord-like elements of the UTROSCTs than in other studies. 7) c-kit may help distinguish metastatic endometrial stromal tumors of the uterus (c-kit negative) from gastrointestinal stromal tumors (c-kit positive). 8) CD34, CD99, and keratin have no or minimal role in this area, but keratin positivity in smooth muscle tumors should not lead to their confusion with epithelial tumors.
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PMID:An immunohistochemical analysis of endometrial stromal and smooth muscle tumors of the uterus: a study of 54 cases emphasizing the importance of using a panel because of overlap in immunoreactivity for individual antibodies. 1191 17

Inflammatory fibroid polyps (IFPs) are rare mesenchymal tumors of the gastrointestinal tract that consist of spindle-shaped stromal cells and an inflammatory infiltrate rich in eosinophils. Their etiology and histogenesis remain unknown. Based on previous reports of their immunoreactivity for CD34 and c-kit biomarkers, IFPs have been thought to be related to gastrointestinal stromal tumors (GISTs). After reviewing the current literature and examining IFPs at the light microscopic level, we evaluated a series of IFPs using an extensive panel of immunohistochemical and in situ hybridization markers in an effort to gain insight into their etiology and histogenesis and to determine their true relationship to GISTs. Sixteen routinely processed IFP specimens (14 gastric, 1 ileal, and 1 rectal) were immunohistochemically stained for antibodies to CD34, HMB-45, desmin, smooth muscle actin, calponin, h-caldesmon, anaplastic lymphoma kinase, S-100 protein, epithelial membrane antigen, c-kit (CD117), stem cell factor (SCF/N19 or kit ligand), p53, bcl-2, cyclin D1, and human herpesvirus-8 (HHV8). In situ hybridization for Epstein-Barr virus-encoded RNA (EBER) was also performed. Ten cases were further evaluated for the dendritic cell markers fascin, CD21, CD23, and CD35. Stromal cells were diffusely positive for CD34 and fascin in all (100%) cases, and these stromal cells were, in addition, immunoreactive for calponin and smooth muscle actin in 88% and 25% of cases, respectively. CD35 was also found to be focally reactive in the stromal cells. Cyclin-D1 was overexpressed in all (100%) IFPs. All other immunohistochemical markers and EBER were negative in the stromal cells. These findings suggest that the proliferating stromal cells in IFPs are of dendritic cell origin, with some cases also exhibiting myofibroblastic features. Absence of c-kit, SCF, and h-caldesmon immunoreactivity fails to support a relationship to GISTs. We also conclude that Epstein Barr virus and HHV8 are unlikely etiologic agents of IFPs. Overexpression of cyclin D1 in all cases suggests that a defect in cell-cycle regulation may be involved in the growth of IFPs.
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PMID:Inflammatory fibroid polyps of the gastrointestinal tract: evidence for a dendritic cell origin. 1470 72

Adenoid cystic carcinoma of the breast is a rare neoplasm whose cribriform architecture may mimic invasive cribriform carcinoma, cribriform ductal carcinoma in situ, and collagenous spherulosis. The diagnosis may be even more challenging in needle core biopsies. Immunohistochemical expression of p63 and c-kit distinguishes adenoid cystic carcinoma from invasive cribriform carcinoma and ductal carcinoma in situ. A formal comparison of the immunophenotype of adenoid cystic carcinoma to collagenous spherulosis has not been reported. Of concern is the overlap in myoepithelial markers between these two entities. Both may express S100, smooth muscle actin, and p63. This overlap may cause diagnostic confusion yet is under-emphasized in the literature. The expression profile of newer myoepithelial markers has not been studied in this setting. We evaluated smooth muscle actin, p63, calponin, smooth muscle myosin heavy chain, as well as c-kit, in nine cases of cribriform pattern adenoid cystic carcinoma of the breast in comparison to 12 cases of collagenous spherulosis. Both entities strongly expressed p63 and smooth muscle actin; in adenoid cystic carcinoma, the basaloid myoepithelial-like tumor cells expressed these markers, but the ductular epithelial cells did not. Neither calponin nor smooth muscle myosin heavy chain was expressed in adenoid cystic carcinoma but both were strongly expressed in collagenous spherulosis. Whereas the ductular epithelial cells of adenoid cystic carcinoma were positive for c-kit in all cases, collagenous spherulosis was negative for c-kit. Positive p63 expression by a cribriform breast lesion is not sufficiently specific to confirm a diagnosis of adenoid cystic carcinoma. A broader panel that includes calponin or smooth muscle myosin heavy chain and c-kit is required to exclude collagenous spherulosis in settings in which the distinctive morphologic features that separate these entities are not conspicuously present. Reliance on p63 or smooth muscle actin alone poses a potential diagnostic pitfall in evaluating cribriform breast lesions.
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PMID:Immunophenotypic overlap between adenoid cystic carcinoma and collagenous spherulosis of the breast: potential diagnostic pitfalls using myoepithelial markers. 1681 Mar 11

Venous injury and attendant venous stenosis are major contributors to the failure of hemodialysis vascular accesses. This report describes the presence of neoangiogenesis in the intima and adventitia of the venous limb of an arteriovenous (AV) fistula in the rat, the latter induced by creating an aortocaval fistula. Immunohistochemistry of the venous limb demonstrated the presence of c-Kit-positive cells lining new microvessels with lumen formation and that these c-Kit-positive cells exhibited either a smooth muscle phenotype as reflected by concomitant expression of calponin, or an endothelial phenotype as reflected by expression of endothelial nitric oxide synthase (eNOS). Western analysis confirmed upregulation of eNOS in the venous limb of the AV fistula. Measurement of systemic concentrations of angiogenic cytokines, namely, monocyte chemotactic protein-1, stromal cell-derived factor-1 (SDF-1), cytokine-induced neutrophil chemoattractant, and VEGF, failed to reveal an increase in these cytokines either at 3 or 10 wk after creation of the AV fistula. The angiogenic cytokines VEGF and SDF-1 were not upregulated in the venous limb of the AV fistula either at 2 or 16 wk. We conclude that in this model of an AV fistula in the rat, neoangiogenesis occurs and is constituted, at least in part, by bone marrow-derived cells, the latter differentiating to exhibit either an endothelial or smooth muscle phenotype. In view of these findings, we suggest that this model may offer an experimental approach by which to explore the evolution and significance of neoangiogenesis in the formation and pathobiology of vascular plaques, and the mechanisms that promote dysfunction of hemodialysis AV fistulas.
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PMID:Neoangiogenesis and the presence of progenitor cells in the venous limb of an arteriovenous fistula in the rat. 1753 82

We report a case of giant gastrointestinal stromal tumor (GIST) of the stomach of 17 cm in diameter detected in an 88-year-old Caucasian female. An en-block resection of the mass requiring gastric and transverse colon resection was carried out. Pathological examination evidenced a smooth multicystic giant gastric GIST measuring 17 x 13 x 9 and weighing 1,630 g. At immunohistochemistry, the specimen was c-kit positive, CD34-positive, SMA-negative S100-negative, desmin-negative, CD31-negative, HMB45-negative, and calponin-negative. It was diagnosed as an uncommitted GIST at high risk for malignancy.
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PMID:Giant gastrointestinal stromal tumor of the stomach in an elderly patient. 1756 23

It is now established that non-contractile cells with thin filopodia, also called vascular interstitial cells (VICs), are constitutively present in the media of many, if not all, blood vessels. The aim of this study was to determine the type of cell lineage to which arterial VICs belong using immunocytochemical, and real-time and reverse transcription PCR (RT-PCR). Using RT-PCR, we compared gene expression profiles of single VICs and smooth muscle cells (SMCs) freshly dispersed from rat middle cerebral artery. Both VICs and SMCs expressed the SMC marker, smooth muscle myosin heavy chain (SM-MHC), but did not express fibroblast, pericyte, neuronal, mast cell, endothelial or stem cell markers. Freshly isolated VICs also did not express c-kit, which is the marker for interstitial cells of Cajal in the gastrointestinal tract. Immunocytochemical labelling of contractile proteins showed that VICs and SMCs expressed SM-MHC similarly to the same degree, but VICs in contrast to SMCs had decreased expression of alpha-SM-actin and very low or no expression of calponin. Real-time RT-PCR was consistent with immunocytochemical experiments and showed that VICs had four times lower gene expression of calponin comparing to SMCs, which may explain VICs' inability to contract. VICs had greater expression than SMCs of structural proteins such as non-muscular beta-actin and desmin. The results obtained suggest that VICs represent a subtype of SMCs and may originate from the same precursor as SMCs, but later develop filopodia and a non-contractile cell phenotype.
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PMID:Interstitial cells from rat middle cerebral artery belong to smooth muscle cell type. 1917 86

Chondroid tumors comprise a heterogenous group of benign to overt malignant neoplasms, which may be difficult to differentiate from one another by histological examination. A group of 43 such tumors was stained with nine relevant antibodies in an attempt to find consistent marker profile(s) for the different subgroups. Archival material from three extraskeletal myxoid chondrosarcomas, five chordomas, five chondromyxoid fibromas, five chondroblastomas and 25 chondrosarcomas was stained with antibodies against osteonectin, bcl-2, cox-2, actin, calponin, D2-40 (podoplanin), mdm-2, CD117 (c-kit) and YKL-40. All 25 chondrosarcomas showed a positive staining reaction for D2-40, none for actin and CD117, and a partial reactivity for bcl-2 (36%). Chondroblastomas (5/5) and chondromyxoid fibromas (2/5) were the only tumors with a positive reaction for actin, and all chondroblastomas (n=5) and extraskeletal myxoid chondrosarcomas (n=3) were positive for bcl-2. In contrast to all other tumors, two of three extraskeletal myxoid chondrosarcomas were also positive for CD17 and negative for osteonectin, cox-2, mdm-2 and actin. All five chordomas were negative for D2-40 and positive for mdm-2 and YKL-40. The diagnosis of chondrosarcoma may be aided by its positivity for D2-40 and YKL-40 and its lack of reactivity for actin and CD117. This should be seen in the light of no reaction for D2-40 in chordomas and a corresponding lack of reaction for osteonectin, cox-2, mdm-2 and actin in extraskeletal myxoid chondrosarcomas. A convincing immunoreactivity for calponin and/or actin in chondromyxoid fibromas and chondroblastomas may also be helpful in differentiating these tumors from chondrosarcomas.
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PMID:Markers aiding the diagnosis of chondroid tumors: an immunohistochemical study including osteonectin, bcl-2, cox-2, actin, calponin, D2-40 (podoplanin), mdm-2, CD117 (c-kit), and YKL-40. 1959 92


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