Expression Of C-kit Gene And Mutation Of The Exon 11 Relate To The Clinical Pathology Of Gastrointestinal Stromal Tumor

Objective:Gastrointestinal stromal tumor(GIST) is increasingly being recognized over the past decade as an independent clinical and pathological entity.GIST is the most common mesenchymal tumors of the gastrointestinal tract, and it accounts for 1%-4% of gastrointestinal tumors. In recent years, the incidence rises in our country. At present, most pathologist and clinical oncologist think all of them have a transfer risk, there is no absolute benign GIST. Conventional chemotherapy or radiation therapy for GIST is almost ineffective, treatment mainly depends on the surgery, but the high rate of recurrence and metastasis can produce a large number of patients survival with tumor often requires the implementation of multiple surgery. So, to research on the major factors affect the biological behavior and prognosis of GIST, gives targeted intervention likely to improve the prognosis. Present agreed that, the occurrence of GIST is the mutation of the c-kit gene. Research shows c-kit gene mutation locus are mainly at exon 9,11,13, and 17, of which exon 11 is the most common. Exon 11 mutation is closely related to the biological behavior, prognosis, drug treatment of GIST. There are many reports on c-kit gene expression, gene mutation and clinicopathological features of GIST, but the results quite different, in particular the relationship of exon 11 mutation and c-kit gene expression with the clinical pathology of GIST are rarely reported.The purpose of this study is to research on the relationship of c-kit gene expression and exon 11 mutations with clinical pathology of GIST, especially on the relationship between exon 11 mutation and c-kit gene expression, for exploring the possibilities of predicting c-kit gene mutations and biological behavior from gene expression levels, and provide a referent parameter for the treatment and prognosis of GIST.Methods:A total 50 specimens (including 5 fresh samples) were selected from the Second Affiliated Hospital of Dalian Medical University between 2005 and 2009. All of them have complete pathological information. Immunohistochemistry, Western-Blot and RT-PCR were used to analyze c-kit gene expression, and c-kit exon 11 mutation was detected by PCR-SSCP. The relationship of c-kit gene expression and exon 11 mutations with clinical pathology, especially the relationship between exon 11 mutation and c-kit expression, were to discussed. Experimental data were analyzed by SPSS 11.5 statistical software.Results:1. KIT protein expression was deteced and higher by immunohistochemistry in poorly differentiated GIST (p<0.05).2. Western blot results showed that expression of KIT mature protein in the high invasion risk GIST (p<0.05).3. c-kit gene exon 11 mutation rate was 52%(26/50), and had a predilection for women aged> 60, maximum tumor diameter> 5cm, and the high risk of GIST (p< 0.05).4.GIST with exon 11 mutation, KIT mature protein expression is higher (p<0.05).Conclusion:1. KIT mature protein, a status of post-translational modification of KIT protein of might play an important role in development of GIST and associated with a high invasion risk of GIST.2. Total expressions of c-kit protein and mRNA were not significantly correlated with clinicopathological features of GIST.3. c-kit gene exon 11 mutation might be an indicator of malignant biologic behavior in GIST.4. c-kit gene exon 11 mutation was correlated to the increase of expression of KIT mature protein.5. Detection of KIT protein expression by immunohistochemistry might have greater values in diagnosis rather than prediction of biological behavior in GIST.