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)

Among gynecologic malignancies, ovarian carcinoma is the most frequent cause of death, with the majority of patients presenting at advanced stage. There is a high rate of recurrence despite first-line chemotherapy. Sarcoma of the uterus, while accounting for a small percent of uterine cancers, is also associated with a high-recurrence rate and poor overall survival. Therefore, the development of novel treatment strategies is paramount. Imatinib mesylate (Gleevec; Novartis Pharmaceuticals Corp., East Hanover, NJ) is a tyrosine kinase inhibitor with activity against abl, c-kit, and platelet derived growth factor receptor (PDGFR), and is approved for the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumor. Preclinical data provides evidence for c-kit and PDGFR expression in ovarian epithelial carcinomas and uterine sarcomas and have led to clinical trials evaluating the use of imatinib in these malignancies. Additionally, inhibition of PDGFR signaling has been proposed as an effective mechanism of chemotherapy by lowering tumor interstitial fluid pressure. Recent data have also suggested benefit with metronomic scheduling of cytotoxic agents at lower doses at more frequent dosing intervals, in combination with other targeted therapies. While activity of this agent remains to be established, further studies of imatinib in gynecologic malignancies are warranted, to demonstrate not only single-agent activity and the enhancement of cytotoxicity of other antineoplastic agents.
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PMID:Imatinib mesylate and its potential implications for gynecologic cancers. 1571 93

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

Previous reports describing Cajal-like interstitial cells in human uterus are contradictory in terms of c-kit immunoreactivity: either negative (but vimentin-positive) in pregnant myometrium, or positive, presumably in the endometrium. The aim of this study was to verify the existence of human myometrial Cajal-like interstitial cells (m-CLIC). Six different, complementary approaches were used: 1) methylene-blue supravital staining of tissue samples (cryosections), 2) methylene blue and Janus green B vital staining (m-CLIC and mitochondrial markers, respectively), and 3) extracellular single-unit electrophysiological recordings in cell cultures, 4) non-conventional light microscopy on glutaraldehyde/osmium fixed, Epon-embedded semi-thin sections (less than 1 microm) stained with toluidine blue (TSM), 5) transmission electron microscopy (TEM), and 6) immunofluorescence (IF). We found m-CLIC in myometrial cryosections and in cell cultures. In vitro, m-CLIC represented approximately 7% of the total cell number. m-CLIC had 2-3 characteristic processes which were very long (approximately 60 microm), very thin (< or =0.5 microm) and moniliform. The dilated portions of processes usually accommodated mitochondria. In vitro, m-CLIC exhibited spontaneous electrical activity (62.4+/-7.22 mV membrane potentials, short duration: 1.197+/-0.04 ms). Moreover, m-CLIC fulfilled the usual TEM criteria, the so-called 'gold' or 'platinum' standards (e.g. the presence of discontinuous basal lamina, caveolae, endoplasmic reticulum, and close contacts between each other, with myocytes, nerve fibers and/or capillaries etc.). IF showed that m-CLIC express CD117/c-kit, sometimes associated with CD34, with vimentin along their processes. In conclusion, we describe myometrial Cajal-like interstitial cells that have affinity for methylene blue and Janus green B vital dyes, fulfill (all) TEM criteria, express CD117/c-kit and have spontaneous electric activity.
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PMID:C-kit immunopositive interstitial cells (Cajal-type) in human myometrium. 1596 60

Endometrium is a highly regenerative adult tissue that undergoes repeated degeneration and regeneration following menarche. Therefore, it is believed that endometrium contains stem and/or progenitor cells in order to compensate for the regeneration of tissue components. We report here that stem-like cells having vasculogenic potential are present in the uterus. Enzymatically extracted cells from murine uteri were characterized and fractionated into four subpopulations by flowcytometry; CD34(+)/45(-) (Ut-34), CD34(-)/45(-) (Ut-DN) and the remaining CD45(+) cell fractions (CD34(+)/45(+) and CD34(-)/45(+) cells). The Ut-34 and Ut-DN fractions were mostly negative for putative endothelial cell (EC) markers, such as CD31, Flk-1, c-kit and VE-cadherin, although the Ut-DN fraction contained 2.8% CD31(+) cells. Ut-DN cells were further divided into CD31(+) and CD31(-) fractions. Three cell populations were obtained from green fluorescence protein (GFP) transgenic mice and were transplanted into injured wild-type mouse skeletal muscle. At 4 weeks after cell transplantation, donor-derived vascular smooth muscle and ECs were observed in the injured recipient muscle. A similar trend was observed in the Ut-34 group, but differentiation into vascular smooth muscle was predominant. In contrast, the Ut-DN/31(+) cell-transplanted group showed preferential differentiation into vascular ECs, thus suggesting that they were relatively committed preexisting ECs. These characteristics were also seen in vitro, in clonal cell cultures. Interestingly, donor derived Ut-DN/31(+), Ut-DN/31(-) and Ut-34 cells could not be identified after bone marrow (BM) transplantation, thus confirming that they are not derived from BM. It therefore appeared that tissue-specific vasculogenic cells are present in the murine uterus and that they exhibit vascular formation, even in different tissue microenvironments.
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PMID:Identification of tissue-specific vasculogenic cells originating from murine uterus. 1631 38

PEComas, occasionally associated with the tuberous sclerosis complex, are defined by the presence of perivascular epithelioid cells that coexpress muscle and melanocytic markers. This family of tumors includes angiomyolipoma (AML), clear cell sugar tumor of the lung (CCST), lymphangioleiomyomatosis (LAM), and very rare tumors in other locations. Because non-AML/non-LAM PEComas are extremely rare and their natural history and prognostic features undefined, we present our experience with 26 PEComas of soft tissue and the gynecologic tract, the largest series to date. We also performed a detailed review of the literature, with special attention to features predictive of clinical behavior. All PEComas exclusive of AML and LAM were retrieved from our consultation files. Immunohistochemistry for pan-cytokeratin (CK), S-100 protein, smooth muscle actins (SMA), desmin, vimentin, HMB45, Melan-A, microphthalmia transcription factor (MiTF), TFE3, CD117, and CD34 was performed. Clinical follow-up information was obtained. Fisher's exact test was performed. The median patient age was 46 years (range, 15-97 years); there was a marked female predominance (22 females, 4 males). Sites of involvement included the omentum or mesentery (6 cases), uterus (4 cases), pelvic soft tissues (3 cases), abdominal wall (2 cases), uterine cervix (2 cases), and vagina, retroperitoneum, thigh, falciform ligament, scalp, broad ligament, forearm, shoulder, and neck (1 case each). The tumors ranged from 1.6 to 29 cm in size (median, 7.8 cm). Tumors were epithelioid (N = 9), spindled (N = 7), or mixed (N = 10). Multinucleated giant cells were present in 18 cases. High nuclear grade was noted in 10 cases, high cellularity in 7 cases, necrosis in 8 cases, and vascular invasion in 3 cases. Mitotic activity was 0 to 50 mitotic figures (MF)/50 high power fields (HPF) (median, 0 MF/50 HPF) with atypical MF in 6 cases. IHC results were: SMA (20/25), desmin (8/22), HMB45 (22/24), Melan-A (13/18), MITF (9/18), S-100 protein (8/24), CK (3/23), vimentin (12/14), TFE3 (5/17), c-kit (1/20), and CD34 (0/7). Clinical follow-up (24 of 26 patients, 92%; median, 30 months; range, 10-84 months) showed 3 local recurrences and 5 distant metastases. At last available clinical follow-up, 2 patients (8%) were dead of disease, 4 patients (17%) were alive with metastatic or unresectable local disease, and 18 patients (75%) were alive with no evidence of disease. No patient in our series had a history of tuberous sclerosis complex. Recurrence and/or metastasis was strongly associated tumor size > median size (8 cm), mitotic activity greater than 1/50 HPF, and necrosis. We conclude that PEComas of soft tissue and gynecologic origin may be classified as "benign," "of uncertain malignant potential," or "malignant." Small PEComas without any worrisome histologic features are most likely benign. PEComas with nuclear pleomorphism alone ("symplastic") and large PEComas without other worrisome features have uncertain malignant potential. PEComas with two or more worrisome histologic features should be considered malignant. Occasional PEComas express unusual markers, such as S-100 protein, desmin, and rarely CK. The role of TFE3 in PEComas should be further studied.
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PMID:Perivascular epithelioid cell neoplasms of soft tissue and gynecologic origin: a clinicopathologic study of 26 cases and review of the literature. 1632 28

Expression of estrogen (ER) and progesterone (PR) receptors was investigated in cultured human normal myometrial cells (non-pregnant uterus, fertile period). The ER and PR expression was studied by immunohistochemistry and immunofluorescence on either myocytes or interstitial Cajal-like cells (ICLC). Only those cells double immunostained for c-kit and steroid receptors were considered as ICLC. ER and/or PR immunoreactivity was localized in ICLC, primarily concentrated at the nucleus level, but it was also observed in the cell body (cytoplasm) and processes. Stronger immunopositive reaction in the ICLC nucleus for PR than for ER was noted. Under our experimental conditions, a clear positive repeatable reaction for steroid receptors could not be detected in myocytes. In conclusion, these data suggest that ICLC could be true hormonal 'sensors', possibly participating in the regulation of human myometrial contractions (via gap junctions with myocytes and/or by paracrine signaling).
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PMID:Interstitial Cajal-like cells (ICLC) as steroid hormone sensors in human myometrium: immunocytochemical approach. 1698 38

The protooncogene c-kit encoding transmembrane tyrosine kinase receptor protein plays an important role in the signal transduction pathway that regulates cellular growth and repair. Gene product KIT overexpression has been shown in a number of different neoplasms, particularly in mastocytosis and gastrointestinal stromal tumours (GIST). The morphologic similarity of uterine mesenchymal tumours and GIST, and the presence of KIT protein in normal uterine tissue, suggests that uterine sarcomas may have the same c-kit overexpression. The purpose of this study was to determine the overexpression of c-kit protein in uterine and ovarian sarcomas. Immunohistochemical staining using a polyclonal anti-c-kit antibody was performed on tissue blocks from 12 carsinosarcomas, 14 leiomyosarcomas, 8 endometrial stromal sarcomas, 2 adenosarcomas, 1 atypical leiomyoma, 1 leiomyoma with limited experience, and 10 leiomyomas. The slides were evaluated by a semiquantitative method. C-kit was positive in 10 of 12 (83%) carcinosarcomas, 10 of 14 (71%) leiomyosarcomas, 6 of 8 75(%) endometrial stromal sarcomas, 1 of 2 (50%) adenosarcomas, 1 leiomyoma with limited experience, and 1 of 10 (10%) leiomyomas. The uterine sarcomas express c-kit, like GISTs. It seems that KIT may have a significant role in the oncogenesis of mesenchymal tumours of the uterus and ovary.
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PMID:C-kit protein expression in uterine and ovarian mesenchymal tumours. 1736 65

Traditional interstitial cells of Cajal (ICC) are present in the digestive tube and are supposed to act as pacemakers and neuromodulators. However, interstitial Cajal-like cells (ICLCs) were found outside the gastrointestinal tract, in various organs (e.g. ureter, bladder, fallopian tube, uterus, pancreas, mammary gland, myocardium etc.) and looking for such ICLC is a priority in our laboratories. We report here unequivocal visual evidence that ICLCs are present in the mesenchymal tissue of the villi from human term placenta. The following methods were used: a. vital staining with methylene blue (cryosections); b. silver impregnation (paraffin sections); c. Epon-embedded sections (approximately 1 microm) of glutaraldehyde/osmium fixed tissue, stained with toluidine blue; d. primary cell cultures (or second-passage cells) to reveal the characteristic, very long, moniliform cell processes and mitochondrial localization at dilations (molecular fluorescence probe: Mito Tracker Green); e. immunofluorescence for c-kit/CD117 marker or other characteristic proteins; f. transmission electron microscopy to establish the identity of ICLC.
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PMID:Human placenta: de visu demonstration of interstitial Cajal-like cells. 1763 51

Gastrointestinal stromal tumor (GIST) usually occurs in the gastrointestinal tract, mainly in the stomach. Recently, GIST arising in extragastrointestinal organs was been reported. This case was a 49-year-old female who was diagnosed as having uterine leiomyoma and pelvic tumor in the rectovaginal septum. The pelvic tumor showed no connection with the uterus and rectum. Grossly, the pelvic tumor was light brown and solid. Cytologically, the tumor cells of the pelvic tumor showed vague interlacing fascicles with spindle/fibrous cytoplasm and elongated nuclei. No necrosis or mitosis was present. Histological findings of the pelvic tumor revealed an interlacing bundle fashioned with one to two mitotic figures per 50 HPE No necrosis was found in the tumor. The tumor cells were positive for CD117 (c-kit protein), CD34, and vimentin by immunohistochemistry, but negative for actin, desmin, and S-100. The tumor was diagnosed as GIST in the pelvic cavity. GIST rarely presents in extragastrointestinal regions such as this case. It is difficult to make a differential diagnosis between GIST and other mesenchymal spindle cell tumors only from a cytologic specimen. A positive reaction for CD117 is useful for the diagnosis of GIST.
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PMID:[Histopathological and cytological findings in a case of gastrointestinal stromal tumor presenting in the pelvic cavity]. 1765 86

An 87-year-old woman underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy for endometrioid adenocarcinoma. At operation, a 4.5-cm partially solid and partially cystic right ovarian mass was identified. Frozen section showed a cytologically bland spindle cell proliferation reminiscent of cellular fibroma. Extensive sampling of the ovarian mass revealed a focus with the classic sieve-like pattern of a Wolffian adnexal tumor that merged with the fibroma-like appearance. The uterus showed well-differentiated, superficially invasive endometrioid adenocarcinoma arising in a background of atypical complex hyperplasia. Given the recent reports implying a therapeutic value for Gleevec (Novartis, Stein, Switzerland) (STI-571) in the treatment of Wolffian tumor of the ovary, paraffin immunostain for CD117 (c-kit) was performed that yielded negative results. Without further therapy, the patient was alive without disease 7 months after surgery. This case demonstrates the heterogeneity of Wolffian tumor of the ovary and shows how crucial sampling is in arriving at the correct diagnosis.
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PMID:Wolffian tumor of the ovary with a prominent spindle cell component: report of a case with brief discussion of unusual problems in differential diagnosis, and literature review. 1841 86


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