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)

Epithelioid gastrointestinal stromal tumors (GISTs) may cause significant diagnostic confusion on fine-needle aspiration (FNA) with carcinomas, neuroendocrine tumors, and melanoma, particularly when metastatic. This study characterizes the cytologic features of nine cases of epithelioid GISTs that were obtained by computerized tomographic guidance in five, by endoscopic ultrasound in three, and from an excised liver tumor in one. Six cases presented as liver masses, one as a perisplenic mass, one as an abdominal mass, and one as a gastric mass. The aspirates revealed mainly single or small clusters of epithelioid cells with a moderate amount of granular to clear cytoplasm, small uniform nuclei with mild to marked nuclear envelope irregularities. Binucleation and intranuclear inclusions were frequent findings. Collagenous stroma was seen in most cases. In three cases, a neuroendocrine tumor was the initial diagnosis. Immunocytochemical staining for c-kit (CD117) was performed on cellblocks in six cases and was positive in five cases. On the subsequent surgical specimen, CD117 was positive in the c-kit-negative cytology case. The diagnosis of GIST should be considered in aspirates of the gastrointestinal tract, liver, mesentery, or abdominal wall mass lesions when epithelioid cells are the predominant cell type. Ancillary studies such as immunohistochemical stains are usually helpful in making a definitive diagnosis.
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PMID:Epithelioid variant of gastrointestinal stromal tumor: Diagnosis by fine-needle aspiration. 1288 40

Several signaling pathways have been recognized in normal c-kit-mediated signal transduction following stem cell factor (SCF) stimulation including Janus kinase (JAK)/signal transducer and activator of transcription (STAT), mitogen-activated protein kinase (MAPK) and phosphoinositol 3-kinase (PI-3 K) pathways. In gastrointestinal stromal tumor (GIST), c-kit activation is considered to play a central role in its tumorigenesis. However, the signal transduction cascades specific for the SCF-independent c-kit activation in GIST remains to be elucidated. In this study, we examined for the expression of the activated form of STAT3 [phospho-STAT3 (tyr 705)] in eleven cases of GIST by immunohistochemistry. All GISTs had strong nuclear and variable cytoplasmic expression of phospho-STAT3 (tyr 705). Survival and proliferation of two established primary GIST cell lines with c-kit exon-11 mutations were then assessed for their response to inhibitors of c-kit (STI-571), JAK 2 (Tyrphostin AG490), MAPK kinase (PD98059) and PI-3 K(LY294002). GIST cells showed significant inhibition of proliferation and apoptosis when treated with STI571 or AG490 but not in cells treated with PD98059 or LY294002. Bcl-2 was expressed in all of the GIST cases (11 out of 11) and was down-regulated in the primary GIST cells following treatment with AG490. This study demonstrates that STAT3 is constitutively activated in GIST and JAK2 blockade leads to tumor growth inhibition and apoptosis indicating the involvement of the JAK/STAT signaling pathway in GIST cellular survival.
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PMID:Analysis of signal transducer and activator of transcription 3 (STAT3) in gastrointestinal stromal tumors. 1289

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors. The molecular etiology is the result of mutations in the c-Kit gene. The mutant c-Kit proteins, which are activated without a stem cell factor, contribute to the tumor development. STI571 selectively inhibits c-Kit, BCR-ABL, and PDGFR tyrosine kinases. Based on this potential to inhibit critical c-Kit function in GISTs, case studies have reported effective outcomes following treatment with STI571. This case report describes a highly effective use of STI571 in a 54-year-old woman with multiple liver metastases from a GIST originating in the duodenum.
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PMID:Effect of a tyrosine kinase inhibitor STI571 in a patient with hepatic metastases from a duodenal gastrointestinal stromal tumor. 1289 63

We describe a case in which segmental resection of the third portion of the duodenum was performed for a gastrointestinal stromal tumor (GIST). A 31-year-old woman was found to have a 3.5 cm hypovascular tumor at the posterior inferior aspect of the pancreatic head. Preoperative duodenal biopsy revealed that the tumor was positive for c-kit and vimentin, and was diagnosed as a duodenal GIST. Segmental resection of the third portion of the duodenum with papilloplasty and duodenojejunostomy was carried out and there were no postoperative complications. Pancreatoduodenectomy is not always necessary in the treatment of a duodenal GIST. This duodenectomy procedure can serve as a less extensive resection for a duodenal GIST located in the third portion of the duodenum.
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PMID:Segmental resection of the third portion of the duodenum for a gastrointestinal stromal tumor: a case report. 1294 65

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. A characteristic genetic alteration in GISTs is constitutive activation of the c-kit proto-oncogene, but alterations in chromosomes 14 and 22 may also play a role in the molecular pathogenesis. In this study, 42 GISTs were analyzed for loss of heterozygosity (LOH) on the long arm of chromosome 22 (22q). Overall, 69% of the tumors studied showed LOH with at least 1 of the 22q markers. Allele losses were compared with tumor mitotic activity, the most commonly used prognostic marker for this tumor. Interestingly, allele deletion at 22q was significantly more frequent in tumors with high mitotic activity (>/= l2 mitoses/10 high-power fields [HPF]) than in tumors with low mitotic activity (< 2 mitoses/HPF)-88% versus 56% (P < 0.01). A total of 26% (11 of 42) of all tumors demonstrated loss of all 22q sites analyzed, consistent with the loss of 1 copy of the entire long arm. Such tumors carried a 4.6-fold (95% confidence interval, 0.5 to 49.8) risk for recurrence compared with tumors with no LOH. LOH was frequently detected at the neurofibromatosis 2 (NF2) tumor-suppressor gene locus at 22q12. Sequencing of the NF2 gene from 5 GISTs did not reveal mutations, however. Furthermore, 16 of 19 tumors (84%) analyzed by immunohistochemistry were positive for the NF2 gene product, merlin. The findings suggest that allelic losses at 22q are associated with high mitotic activity and recurring disease, and that alterations in the NF2 gene are unlikely to participate in the pathogenesis of GIST.
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PMID:Chromosome 22q alterations and expression of the NF2 gene product, merlin, in gastrointestinal stromal tumors. 1456 82

Gastrointestinal stromal tumors (GIST/GIPACT) are the most common mesenchymal tumors of the human gastrointestinal (GI) tract and are characterized by the constant immunohistochemical expression of CD117. In recent years, sporadic and germ line mutations in the c-kit gene have been described in GIST/GIPACT tumors, resulting in a constitutive activation of the gene. The most prevalent mutation is located in exon 11 of the c-kit gene, involved in the transcription of the juxta-membrane domain of the c-kit protein. There are conflicting reports with respect to the association between exon 11 mutations and the biological behavior of GIST/GIPACT tumors. This work studies eight patients with tumors diagnosed as GIST/GIPACT, both morphologically and immunohistochemically for CD117, CD34, a-smooth muscle actin, desmin and S-100 protein primary antibodies. The DNA of the eight cases was also studied by PCR for mutation of exon 11 of the c-kit gene. All cases were CD117 positive, but only two showed mutation of exon 11. These last two cases did not show morphological characteristics of malignancy. The most aggressive case, with early death of the patient, did not show the mutation. In conclusion, there was no correlation between the mutation of exon 11 of the c-kit gene and the malignant behavior of GIST/GIPACT tumors in our series.
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PMID:Characterization of GIST/GIPACT tumors by inmunohistochemistry and exon 11 analysis of c-kit by PCR. 1458 63

We report the case of a malignant, primary, hepatic gastrointestinal stromal tumor (GIST) that was resected from the liver of a 79-year-old woman. To our knowledge, this is the first primary, hepatic GIST on record. The tumor expressed CD117 (c-Kit protein) and vimentin and had the ultrastructural features of GISTs. Sixteen months after partial hepatectomy and resection of the tumor, a hilar lymph node metastasis was found. The metastatic tumor had the same morphologic features as the primary tumor, but in addition it contained numerous multinucleated giant cells. This case shows that GIST can occur as a primary liver tumor, and accordingly, we point out that not all hepatic tumors with a GIST phenotype should be automatically considered to be metastases from a primary gastrointestinal site.
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PMID:Primary malignant gastrointestinal stromal tumor of the liver. 1463 69

Gastrointestinal stromal tumour (GIST) till recently were non-responsive to all chemotherapy agents. With the advent of c-kit, diagnosis of GIST has become more specific. STI-571, a tyrosine kinase, has become one of the first targeted therapeutic agent tobe active in solid tumour. At present it is the only agent with substantial activity in GIST.
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PMID:Gastrointestinal stromal tumour--a paradigm shift in management of solid tumours. 1465 Nov 44

The growing understanding of the epigenetic changes associated with cancer, including aberrant promoter methylation of tumor suppressor genes that afford selective growth advantages to human neoplasms, suggests that the characterization of gene methylation patterns among gastrointestinal stromal tumors (GISTs) may be useful for predicting tumor behavior. Thirty-eight c-kit-positive gastric stromal tumors were subjected to methylation-specific polymerase chain reaction (MSP) to detect promoter methylation associated with 11 candidate tumor suppressor genes (p16/INK4a, APC, MGMT, hMLH1, p73, E-cadherin, RAR-beta, RASSF1A, RB, ER, and DAPK), established to have a role in tumorigenesis of several solid human organs. Aberrant methylation of any of the 11 candidate tumor suppressor genes was detected in 84% of all GISTs. In decreasing order of frequency, the six most commonly methylated genes were: MGMT (47%), p16 (45%), RASSF1A (40%), E-cadherin (37%), hMLH1 (34%), and APC (31%). For all of the GISTs, promoter methylation was less reliable than tumor mitotic rate in predicting 5-year tumor-free survival for the GISTs; however, E-cadherin methylation was a multivariate prognostic factor for early recurrence of GISTs (50% at 2 years; P=0.030). Among the mitotically active (>5 per 50 high-power field), histologically indistinguishable GISTs, E-cadherin methylation was an independent predictor of tumor-related mortality: 5-year disease-free survival was worse for the E-cadherin methylated GISTs (19%) compared to the E-cadherin unmethylated tumors (71%; P=0.010). Detection of methylation within selected genes may afford a reliable and accurate molecular marker system for predicting neoplastic behavior among GISTs. This study supports the methylation status of E-cadherin as a prognostic marker for early GIST recurrence and survival.
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PMID:Tumor suppressor gene hypermethylation as a predictor of gastric stromal tumor behavior. 1467 10

A 59-year-old man with bloody stools, and previously diagnosed with sigmoid colon carcinoma, visited our hospital. Preoperative abdominal ultrasonography (US) showed another tumor, with an uneven irregular surface, measuring about 9 x 5 cm, below the left hypochondrium. The tumor consisted of several cysts. Abdominal computed tomography (CT) showed a multicystic tumor attached to the stomach, and its septum and marginal region were intensely stained on contrast imaging. On magnetic resonance imaging (MRI), low and markedly high signals were revealed in the tumor on T1-weighted and T2-weighted sequences, respectively. Contrast imaging of the upper digestive tract showed extramural compression of the greater curvature of the antral stomach by the tumor. The tumor was partially imaged by endoscopic ultrasonography (EUS), but continuity to the stomach was not confirmed. On abdominal angiography, the tumor was slightly stained via the gastroepiploic arteries. Surgical treatment was performed to excise both the gastric tumor and the sigmoid colon carcinoma. The gastric tumor was removed with gastric wall tissue where the tumor was attached to a 2-cm pedicle. It was multicystic, contained watery fluid, and had a smooth outer surface. Histologically, the tumor consisted of multiple irregular cysts without epithelial lining, and solid epitheloid cell nests in between. The tumor cells had clear or eosinophilic cytoplasm and round nuclei. No mitotic figures were seen. The tumor cells in the pedicle were connected with the muscularis propriae of the stomach. Immunohistochemistry showed c-kit-positive, CD34-positive smooth muscle actin (SMA)-negative, and S-100-negative staining of tumor cells. The final diagnosis was gastrointestinal stromal tumor (GIST).
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PMID:Exophytic pedunculated gastrointestinal stromal tumor with remarkable cystic change. 1471 58


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