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 expression of the c-kit gene product has been examined in normal mast cells, mast cell neoplasms, and basophil/mast cell precursors obtained from patients with chronic myelogenous leukaemia (CML). Formalin-fixed, paraffin-embedded sections or smears fixed with formalin vapour were studied by immunohistochemical methods, using a polyclonal antibody against the c-kit gene product. Normal and neoplastic mast cells showed a positive immunoreaction for c-kit gene product, but neoplastic basophil/mast cell precursors from CML patients lacked c-kit gene product by immunohistochemical and flow cytometric methods, even in cells having mast cell granules, together with or without basophil granules. Mast cell tryptase was, however, expressed in normal and neoplastic mast cells and basophil/mast cell precursors containing mast cell granules. In addition, cells of monocyte/macrophage lineage lacked c-kit gene product. These findings indicate that the c-kit gene product may play an important role in the development and function of mast cell but not of cell of basophil and monocyte/macrophage lineage.
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PMID:Expression of the c-kit gene product in normal and neoplastic mast cells but not in neoplastic basophil/mast cell precursors from chronic myelogenous leukaemia. 749 Jun 80

The stem cell factor/c-kit tyrosine kinase receptor pathway has been shown to be important for tumor growth and progression in several cancers, including mast cell diseases, gastrointestinal stromal tumor, acute myeloid leukemia, small cell lung carcinoma, and Ewing sarcoma. Studies using the oral agent STI-571 (Gleevec, Novartis), an inhibitor of the tyrosine kinases bcr-abl, c-kit, and PDGFR, have shown significant responses in patients with chronic myelogenous leukemia and gastrointestinal stromal tumor. With the aim of identifying additional groups of tumors that may use the stem cell factor/c-kit pathway and secondarily may be responsive to STI-571 treatment, this study surveyed 151 primary tumors from patients treated at St. Jude Children's Research Hospital for immunohistochemical expression of c-kit. Formalin-fixed, paraffin-embedded sections were stained with rabbit polyclonal anti-human c-kit (CD117, Dako) using standard avidin-biotin-peroxidase complex technique, antigen retrieval, and an automated stainer. Strong, diffuse staining for c-kit was seen in a proportion of synovial sarcomas, osteosarcomas, and Ewing sarcomas. Strong, diffuse staining was less common in neuroblastomas, Wilms' tumors, and rhabdomyosarcomas and was negative in alveolar soft part sarcomas and desmoplastic small round cell tumors. Tumors with strong, diffuse staining for c-kit in a pattern similar to gastrointestinal stromal tumor may represent suitable targets for new therapeutic agents.
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PMID:C-kit expression in pediatric solid tumors: a comparative immunohistochemical study. 1191 27

Adenoid cystic carcinoma (ACC) is characterized by persistent, relentless growth and a high rate of eventual metastasis. In contrast, polymorphous low-grade adenocarcinoma (PLGA) has a much lower risk of recurrence and rarely metastasizes. The histologic patterns of these two neoplasms can be similar. Expression of c-kit, a transmembrane receptor tyrosine kinase, has recently been reported to be expressed in ACC but not PLGA. Expression of galectin-3, a nonintegrin beta-galactosidase-binding lectin, has been reported to be significant in PLGA and decreased in ACC.Formalin-fixed paraffin-embedded tissue from 9 ACC and 14 PLGA were immunostained for c-kit and galectin-3. Cases were scored as 1+ (5-25% positive), 2+ (26-50% positive), or 3+ (>50% positive). C-kit was expressed by 100% of ACC (3+: 7 cases; 2+: 1 case; 1+: 1 case) and by 57% of PLGA (2+: 2 cases; 1+: 6 cases). In all but one ACC, c-kit expression was confined to the inner cell layer. C-kit expression was also noted in the intercalated duct epithelium of the salivary glands and the acinar cells of the lacrimal gland. Galectin-3 was expressed in 8 of 9 cases of ACC and 14 of 14 cases of PLGA. The results of this, the first study to compare c-kit and galectin-3 expression in ACC and PLGA, suggest that c-kit expression characterizes ACC, but not PLGA. Galectin-3 immunohistochemistry does not have a role in the differentiation of ACC and PLGA. C-kit immunostaining may be a valuable adjunctive tool for this differential diagnosis, particularly in the setting of a limited biopsy. Our finding of different patterns of c-kit expression in tubular and solid variants of ACC supports the concept of solid variant ACC as a high-grade tumor, with progression toward an entirely "inner cell" phenotype.
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PMID:C-kit expression distinguishes salivary gland adenoid cystic carcinoma from polymorphous low-grade adenocarcinoma. 1211 4

Recent studies have suggested that the presence of a c-Kit/c-Kit ligand autocrine loop may be an important regulator of proliferation and progression of human colorectal cancer, capable of affecting the prognosis of these patients. If present, the c-Kit alteration may provide a suitable target for therapy, similar to what has been observed in gastrointestinal stromal tumors. To determine the incidence of c-Kit expression in human colorectal carcinomas, we studied the immunohistochemical c-Kit expression in a selection of 126 colorectal carcinomas of different stage, using stage-oriented human cancer tissue microarrays. Formalin-fixed, paraffin-embedded tissues of each case were immunostained using the avidin-biotin-peroxidase method and the antihuman c-Kit (CD117) rabbit polyclonal antibody. High cytoplasmic c-Kit staining (Allred score of 7-8) was observed in 1.6% of the colon carcinoma patients evaluated. The c-Kit-positive tumors were poorly differentiated carcinomas arising at the anorectal junction. The remaining tumors revealed no detectable expression of c-Kit. Twenty-seven non-neoplastic tissues, normal colonic mucosa, and adenomas were also CD117 negative. We show the rare expression of c-Kit in normal and neoplastic colorectal tissues, suggesting that routine screening for c-Kit by immunohistochemistry to identify c-Kit-positive carcinomas may be cost ineffective. However, further study of c-Kit expression in poorly differentiated colon cancers may be useful since these generally chemoresistant tumors may respond to therapy with inhibitor compounds directed against c-Kit.
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PMID:Immunohistochemical staining for c-Kit (CD117) is a rare event in human colorectal carcinoma. 1455 11

Recently, therapies targeting signaling pathways involved in the pathogenesis of different tumors have been developed. Studies have shown that the tyrosine kinase inhibitor STI-571 (Gleevec) is used successfully against tumors expressing the c-kit oncogene, such as gastrointestinal stromal tumors (GISTs). A recent in vitro study also demonstrated an antiproliferative effect of STI-571 on small-cell lung cancer (SCLC) cell lines. To determine the expression of c-kit in SCLC, we retrospectively analyzed presence of c-kit by immunohistochemistry in biopsy samples from patients with SCLCs. Formalin-fixed, paraffin-embedded archival tissue samples from 30 SCLCs were stained with an antibody directed against c-kit (CD117) by immunohistochemistry. Thirty cases of SCLCs, including 17 males (age 44 to 89) and 13 females (age 21 to 85), were examined. Sixteen of 30 (53.3%) SCLCs showed c-kit expression. Kaplan-Meier survival analysis with a log-rank test revealed that patients with c-kit expression had a tendency toward lower survival than c-kit-negative patients (median survival, 6 months versus 31 months, P =.062). Based on previously established anti-c-kit effects of STI-571 on SCLC cell lines and our findings, clinical trials may be considered for selected SCLC patients with c-kit expression. Furthermore, determination of c-kit in SCLC may have a prognostic value in SCLC patients.
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PMID:Analysis of c-kit protein expression in small-cell lung carcinoma and its implication for prognosis. 1450 52

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin that is associated with a high incidence of recurrence and metastasis. The therapeutic arsenal for this malignancy is limited and once it spreads, there is no effective treatment. c-kit expression has been demonstrated previously in primary MCCs thus raising the possibility of treating MCCs with imatinib mesylate, the tyrosine kinase inhibitor that has shown promise in the management of c-kit expressing tumors. In this study we examine 25 additional primary MCCs and also 6 of their lymph node metastases. Formalin-fixed, paraffin-embedded tissues were stained immunohistochemically with an antibody directed against the KIT receptor. Percentage and intensity of staining were analyzed semiquantitatively using a three-tiered system. Twenty-one of the 25 (84%) primary tumors stained positively for KIT, of which 14 (67%) showed widespread positivity. Five of the 6 lymph nodes (83%) were similarly positive. High mitotic rate and vascular invasion in the primary tumors tended to be associated with prominent staining in the lymph node metastases. No association was found between c-kit expression and outcome. We confirm that the majority of primary MCCs express c-kit and further find that metastases are positive for the KIT receptor as well. Thus, c-kit expression may be an early event in the transformation of MCC, but not a marker for tumor progression.
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PMID:c-kit expression in primary and metastatic merkel cell carcinoma. 1561 26

Protein tyrosine kinases (TKs) are overexpressed in many carcinomas and sarcomas. We studied the expression of the following TKs in head and neck squamous cell carcinoma (HNSCC): platelet-derived growth factor receptor (PDGFR), c-kit, epidermal growth factor receptor (EGFR), and a serine-threonine kinase, Akt. Formalin-fixed, paraffin-embedded tumor blocks from 44 consecutive patients with primary HNSCC and 5 specimens of benign pharyngeal and laryngeal mucosa were retrieved for immunohistochemical analysis. Of the specimens, 38 had enough material to stain for all 4 antibodies. The study included 21 pharyngeal (base of tongue, 14; tonsil, 6; soft palate, 1), 16 laryngeal, and 1 floor of the mouth carcinoma. All 4 kinases in the tumor samples were expressed highly (PDGFR, 95%-100%; EGFR, 38%-43%; c-kit, 50%-86%; p-Akt, 57%-81%), with EGFR, c-kit, and p-Akt significantly higher than in benign samples. None of the kinase expressions correlated with disease-free survival. The expression of the kinases raises the possibility of treatment of HNSCC by tyrosine and serine-threonine kinase inhibitors.
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PMID:Expression of protein tyrosine kinases in head and neck squamous cell carcinomas. 1701 96

The c-kit gene encodes a transmembrane receptor (KIT) with tyrosine kinase activity which is a specific target for anti-cancer therapy. We investigated KIT expression in a group of patients with early-stage malignant melanoma. Primary tumour specimens obtained from 261 radically resected patients with stage I and II malignant melanoma were examined for KIT expression. Formalin-fixed, paraffin embedded tissues were stained with the polyclonal rabbit anti-human anti-KIT antibody (Dako Cytomation Inc., Carpenteria, California, USA). Patients were classified into four groups according to the level of expression (0%, <30%, 30-60% and >60%). Univariate and multivariate analyses examining the impact of KIT expression, Breslow thickness, Clark level and microscopic ulceration on disease-free survival were performed. Within the population of 261 patients with early-stage melanoma with 62 recurrences during a follow-up of 64 months, KIT expression was found in 144 cases (55%). KIT was expressed in more than 60% of cells in 20 patients (8%), in 30-60% of cells in 64 patients (24%) and in less than 30% of cells in 60 patients (23%). KIT expression was not found in 117 patients (45%). In univariate analyses, the influence of KIT expression on disease-free survival was not proven (P=0.4956; log-rank test). Increasing Breslow thickness, a higher Clark level, the presence of microscopic ulceration and a higher stage were significantly associated with a shorter disease-free survival (P<0.0001; log-rank test in all cases). In multivariate analysis, Breslow thickness, stage and KIT expression were significant negative prognostic factors for a shorter disease-free survival (P<0.0001, P=0.0028, P=0.0488, respectively; stepwise Cox regression model). It can be concluded that KIT is expressed in more than one-half of early-stage malignant melanoma. KIT may serve as an additive prognostic factor to Breslow thickness and stage within the tested population. The therapeutic impact of KIT expression in malignant melanoma is uncertain. Results of ongoing pilot phase II studies may validate the efficacy of imatinib mesylate in malignant melanoma expressing KIT.
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PMID:KIT receptor is expressed in more than 50% of early-stage malignant melanoma: a retrospective study of 261 patients. 1603 2

KIT is expressed in most gastrointestinal stromal tumors, and they usually show c-kit aberrations (most frequently deletions or deletions coexisting with a single or multiple point mutations). Recently, several studies regarding KIT expression in gynecologic tumors have been reported; however, their outcomes were not consistent. In this study, we immunohistochemically examined KIT expression in sarcomas of the female genital tract and studied the existence of c-kit aberrations to elucidate the characteristics of KIT-positive tumors in the gynecologic region. Formalin-fixed, paraffin-embedded tissues from 25 surgically resected and 1 biopsy specimen from 26 patients were used. Histological diagnoses included 14 uterine leiomyosarcomas, 6 carcinosarcomas, 5 endometrial stromal sarcomas, and 1 vaginal epithelioid sarcoma. Immunohistochemical studies were performed using anti-KIT polyclonal antibody. Only four of the above tumors (15%) were positive for KIT, all of which were carcinosarcomas. Specific KIT immunoreactivity was observed in the only carcinomatous components in one case, in the only sarcomatous component in two cases, and in the both components in one case. However, none of the cases showed c-kit aberrations in exons 9, 11, 13, and 17. Judicious decision is mandatory before applying Imatinib therapy to KIT-positive gynecologic tumors.
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PMID:Immunohistochemical evaluation of KIT expression in sarcomas of the gynecologic region. 1630 88

Detection of activating c-kit mutation D816 V is one of five criteria for the diagnosis of systemic mastocytosis (SM). The aims of this study were to (I) establish molecular methods for the detection of these mutations in paraffin-embedded biopsies, (II) determine the frequency of these mutations in mastocytoses and control tissues, (III) determine the frequency of these mutations in laser-microdissected lesional and nonlesional mast cells (MC), and (IV) investigate these matutions as a marker for clonality in cases with SM and associated clonal hematologic non-mast cell lineage diseases (SM-AHNMD). Formalin-fixed and paraffin-embedded biopsies of 48 patients with cutaneous mastocytosis (CM), 55 cases with various forms of SM, and 239 controls were investigated by PNA-mediated PCR-clamping. In addition, nested PCR amplified DNA of pooled microdissected single mast cells (MC) was investigated by melting point analysis. Activating c-kit mutation codon 816 mutations were detected in 38 % (18/48) of CM, in 91% (50/55) of SM, in 5 % (2/39) of MC hyperplasia and in none of 200 hematologic non-MC neoplasias. c-kit mutations were detected significantly more frequent in lesional MC as compared to non-lesional MC (p = 0,003). In 6/15 (40 %) cases with SM-AHNMD the same c-kit mutations were detected in microdissected MC and AHNMD cells. This study underlines the concept of the actual WHO classification of mastocytoses. By establishing methods for the detection of c-kit codon 816 mutations in paraffin-embedded tissues, the pathologist holds a central position in the diagnosis of systemic mastocytoses.
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PMID:[Molecular pathological analysis of neoplastic mast cells with regard to the actual WHO classification of mast cell neoplasias]. 1786 1


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