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Expression of C-kit Gene and Mutation of the Exon 11 Relate to the Clinical Pathology of Gastrointestinal Stromal Tumor

Author: JiRongWei
Tutor: WangLiFen
School: Dalian Medical University
Course: Pathology and Pathophysiology
Keywords: Gastrointestinal stromal tumors c-kit gene expression Exon 11 mutations Clinical and pathological features
CLC: R735
Type: Master's thesis
Year: 2010
Downloads: 47
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Abstract

Objective: gastrointestinal stromal tumor (gastrointestinal stromal tumor, GIST) gradually over the past decade is the understanding of the independent clinical pathological entity, which includes the past, most of the gastrointestinal leiomyoma, leiomyosarcoma, schwannoma, is the most common gastrointestinal mesenchymal tumors, accounting for 1% to 4% of the tumors of the gastrointestinal tract, its incidence in recent years has tended to increase. Currently, most pathologists and clinical oncologists that have a risk of transfer of all GIST, only low-risk malignant GIST, there is no absolute benign GIST. GIST to conventional chemotherapy and radiotherapy extremely insensitive, treatment mainly depends on the surgery, but a higher recurrence and metastasis rate, with survival in patients often need multiple surgeries on tumor implementation. Therefore, actively study the main factors that affect the the GIST biological behavior and prognosis, given targeted intervention may improve the prognosis. Agreed that GIST pathogenesis of the proto-oncogene c-kit mutations lead to sustained activation of tyrosine kinases, cell proliferation, differentiation runaway due. Studies have shown that the c-kit gene mutation in exon 9,11,13,17, which is outside of exon 11 is the most common. Exon 11 mutations and biological behavior of GIST, prognosis, and closely related to the effects of drug treatment. Gene expression and gene mutation of c-kit and the relationship between the clinical and pathological features of GIST study reported more, but the results are quite different, especially exon 11 mutations in the c-kit gene expression and their relationship with the GIST clinical pathology A few studies. The purpose of this study is the protein levels and mRNA transcription level of gastrointestinal stromal tumor expression of c-kit gene and exon 11 mutations with clinicopathological relationship, especially between exon 11 mutations and gene expression of c-kit investigate the relationship between gene expression (protein and mRNA) levels predict the likelihood of the c-kit gene mutations and tumor biological behavior, provide a reference for the treatment and prognosis of GIST. Methods: 2005-2009 Second Affiliated Hospital of Dalian Medical University pathological data integrity, a clear diagnosis of GIST specimens of 50 patients (5 cases of specimens collected fresh samples of tissue). Immunohistochemistry, Western-Blot and semi-quantitative RT-PCR was used to detect the expression of c-kit gene; c-kit exon 11 by polymerase chain reaction - single strand conformation polymorphism (PCR-SSCP) method of screening mutation cases, analysis of the relationship between the expression of c-kit gene and exon 11 mutations in GIST clinical pathological features; explore the c-kit exon 11 mutations of c-kit gene expression between. The experimental data are processed using SPSS11.5 statistical analysis software. Results: 1, immunohistochemistry was detected by the KIT protein expression in poorly differentiated GIST higher intensity (p lt; 0.05): Western blot results found that the mature protein in high invasion KIT expression in the degree of risk GIST higher (p lt; 0.05); 3, c-kit gene in exon 11 mutation rate was 52% (26/50) occurred in women, maximum tumor diameter gt; 5cm, the mitotic counts gt; 5 and in highly invasive risk GIST. in sub-11 mutation rate (p lt; 0.05); 4, exon 11 mutant GIST mature KIT protein expression (p lt; 0.05). Conclusions: 1-KIT KIT protein post-translational modified forms mature protein may occur in GIST, play an important role in the development of highly invasive and GIST dangerous biological behavior. KIT protein overall expression levels of c-kit gene mRNA expression levels and GIST clinical and pathological features no significant relationship. 3, c-kit exon 11 mutations in GIST malignant behavior of indicators. 4, c-kit gene in exon 11 mutations with mature KIT protein expression levels increased to some extent. 5 Immunohistochemical detection of KIT protein expression intensity greater than the determination of the value of its biological behavior of the diagnostic value of GIST.

Expression of C-kit Gene and Mutation of the Exon 11 Relate to the Clinical Pathology of Gastrointestinal Stromal Tumor

Abstract

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