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Gastric GIST (gastric + gist)

Distribution by Scientific Domains
Medical Sciences100%
Distribution within Medical Sciences
Pathology60%
Oncology & Radiotherapy40%

Selected Abstracts

Clinical significance of oncogenic KIT and PDGFRA mutations in gastrointestinal stromal tumours

HISTOPATHOLOGY, Issue 3 2008
J Lasota
Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Despite clinicopathological differences, GISTs share oncogenic KIT or platelet-derived growth factor-alpha (PDGFRA) mutations. Imatinib, KIT and PDGFRA inhibitor, has been successfully used in the treatment of metastatic GISTs. There are primary KIT or PDGFRA mutations diagnosed before imatinib treatment, linked to GIST pathogenesis, and secondary mutations detected during treatment, causing drug resistance. KIT exon 11 mutations are the most common. Gastric GISTs with exon 11 deletions are more aggressive than those with substitutions. KIT exon 11 mutants respond well to imatinib. Less common KIT exon 9 Ala502_Tyr503dup mutants occur predominantly in intestinal GISTs and are less sensitive to imatinib. An Asp842Val substitution in exon 18 is the most common PDGFRA mutation. GISTs with such mutation are resistant to imatinib. PDGFRA mutations are associated with gastric GISTs, epithelioid morphology and a less malignant course of disease. GISTs in neurofibromatosis 1, Carney triad and paediatric tumours generally lack KIT and PDGFRA mutations. Secondary KIT mutations affect exons 13,17. GISTs with secondary mutations in exon 13 and 14 are sensitive to sunitinib, another tyrosine kinase inhibitor. KIT and PDGFRA genotyping is important for GIST diagnosis and assessment of sensitivity to tyrosine kinase inhibitors. [source]

Hereditary gastrointestinal stromal tumors sharing the KIT Exon 17 germline mutation p.Asp820Tyr develop through different cytogenetic progression pathways

GENES, CHROMOSOMES AND CANCER, Issue 2 2010
Isabel Veiga
Hereditary gastrointestinal stromal tumor (GIST) syndrome is a rare autosomal dominant genetic disorder originated by germline mutations in the KIT or PDGFRA genes. We report the third family with hereditary predisposition to GIST due to the KIT Exon 17 germline mutation p.Asp820Tyr and characterize the cytogenetic progression pathways followed by different GIST sharing the same primary genetic event, using a combination of chromosome banding, comparative genomic hybridization (CGH), and fluorescence in situ hybridization (FISH) analyses. The missense mutation p.Asp820Tyr was detected in the proband's rectal and gastric GIST, as well as in his aunt's GIST epiplon metastasis. The mutation p.Asp820Tyr was subsequently also found in the proband's peripheral blood DNA, as well as in that of 4 of 10 relatives thus far analyzed. CGH analysis revealed loss of 14q and 15q in the proband's gastric lesion, whereas FISH analysis of the proband's rectal GIST did not detect loss of 14q and 15q, but instead loss of 4q and 22q and gain of 20q, indicating that the two tumors were independent GIST. Chromosome banding and CGH analyses of the aunt's GIST epiplon metastasis revealed multiple cytogenetic alterations, including 1p loss, but none in common with the two proband's GIST. We conclude that, although the patients share the same KIT Exon 17 germline mutation, the multiple GIST analyzed followed different pathogenetic progression pathways, each of which did not significantly differ from what has been described in sporadic GIST. © 2009 Wiley-Liss, Inc. [source]

Correlation of enhanced cell turnover with prognosis of gastrointestinal stromal tumors of the stomach: Relevance of cellularity and p27Kip1

PATHOLOGY INTERNATIONAL, Issue 12 2006
Yuta Nemoto
The aim of the present study was to determine whether expression of molecules associated with cell cycle regulation and apoptosis might reflect tumor grade and patients' prognosis of gastrointestinal stromal tumor (GIST). Forty-nine cases of gastric GIST were divided into three grades; low, intermediate, and high risk. Ki-67, cyclin A, cyclin D1, cyclin E, p16Ink4, p21Waf1, p27Kip1, cyclin-dependent kinase (cdk)2, cdk4 and single-strand DNA (ssDNA) were immunohistochemically stained and assessed. Ki-67, ssDNA, cyclin A and cdk2 had higher labeling indices (LI) in high-risk than in low-risk cases. Cyclin E expression was greater in the intermediate- than in the low-risk grade. On Kaplan,Meier analysis, tumor size, necrosis, cellularity, Ki-67, ssDNA, and cyclin A LI were significantly correlated with disease-free survival. Necrosis, cellularity, and Ki-67 LI were significant as prognostic factors on univariate, and Ki-67 LI on multivariate Cox hazard tests. Within the high-risk grade, high cellularity and low p27Kip1 subgroups had the worst prognosis. The histological grade is related to cell turnover, assessed in terms of Ki-67, ssDNA, cyclin A, cyclin E, and cdk2 levels. Ki-67, ssDNA, and cyclin A are useful for prediction of prognosis, with cellularity and p27Kip1 expression as further prognostic factors in high-risk cases. [source]

Clinical significance of oncogenic KIT and PDGFRA mutations in gastrointestinal stromal tumours

HISTOPATHOLOGY, Issue 3 2008
J Lasota
Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Despite clinicopathological differences, GISTs share oncogenic KIT or platelet-derived growth factor-alpha (PDGFRA) mutations. Imatinib, KIT and PDGFRA inhibitor, has been successfully used in the treatment of metastatic GISTs. There are primary KIT or PDGFRA mutations diagnosed before imatinib treatment, linked to GIST pathogenesis, and secondary mutations detected during treatment, causing drug resistance. KIT exon 11 mutations are the most common. Gastric GISTs with exon 11 deletions are more aggressive than those with substitutions. KIT exon 11 mutants respond well to imatinib. Less common KIT exon 9 Ala502_Tyr503dup mutants occur predominantly in intestinal GISTs and are less sensitive to imatinib. An Asp842Val substitution in exon 18 is the most common PDGFRA mutation. GISTs with such mutation are resistant to imatinib. PDGFRA mutations are associated with gastric GISTs, epithelioid morphology and a less malignant course of disease. GISTs in neurofibromatosis 1, Carney triad and paediatric tumours generally lack KIT and PDGFRA mutations. Secondary KIT mutations affect exons 13,17. GISTs with secondary mutations in exon 13 and 14 are sensitive to sunitinib, another tyrosine kinase inhibitor. KIT and PDGFRA genotyping is important for GIST diagnosis and assessment of sensitivity to tyrosine kinase inhibitors. [source]

A nonrandom association between gastrointestinal stromal tumors and myeloid leukemia,

CANCER, Issue 3 2008
Markku Miettinen MD
Abstract BACKGROUND. Gastrointestinal stromal tumors (GISTs) are KIT-positive mesenchymal tumors of the gastrointestinal tract that are driven by activated KIT-signalling or platelet-derived growth factor receptor-, (PDFGRA) signaling. These tumors most commonly occur in the stomach and small intestine and encompass a clinical spectrum from benign to malignant. In the current study, the authors examined long-term follow-up data of 1892 GIST patients from the U.S. BACKGROUND. Nine patients (2 with gastric GISTs and 7 with GISTs of the small intestine) developed myeloid leukemia. There were 6 patients (4 women and 2 men) with acute myeloid leukemia (AML), including 1 case of promyelocytic and 1 case of myelomonocytic leukemia, and 3 patients (2 men and 1 woman) with chronic myeloid leukemia (CML). RESULTS. The leukemias developed 1.7 to 21 years after the GIST (median interval, 6 years). None of the GIST patients had received radiotherapy or chemotherapy prior to the leukemia diagnosis. Eight of 9 patients died of leukemia, and none died of GIST. All but 1 GIST case was found to have a low mitotic rate (0,1 per 50 high-power fields); however, tumor size varied from 3 to 18 cm (median, 4.5 cm). Standardized incidence ratios (SIRs) and their 95% confidence intervals (95% CIs) were calculated comparing the incidences of AML/CMLs in GIST patients with those in the 2000 through 2003 U.S. population. In GIST patients, the risk of AML was found to be significantly higher for women (SIR of 5.14; 95% CI, 1.34,11.4) and overall (SIR of 2.96; 95% CI, 1.07,5.8). There was a slightly increased risk for CML, but this was not statistically significant (SIR of 3.71; 95% CI, 0.7,9.1). CONCLUSIONS. Additional epidemiologic, clinical, and pathogenetic studies are needed to understand the apparent nonrandom association between GIST and myeloid leukemia. Cancer 2008. © 2007 American Cancer Society. [source]