胃肠间质瘤c-kit基因表达和外显子11突变与临床病理关系的研究

Relationship of c-kit expression and mutation in the exon 11 to the clinicopathological features in gastrointestinal stromal tumor

目的探讨胃肠间质瘤c-kit基因表达和外显子11突变与临床病理的关系。方法选取病理资料完整、诊断明确的胃肠间质瘤(gastrointestinal stromal tumor,GIST)标本60例(其中15例标本同时收集新鲜标本组织),用免疫组织化学(En Vision二步法)及Western-blot检测KIT蛋白表达;半定量RT-PCR方法检测c-kit基因的表达;通过聚合酶链式反应-单链构象多态(PCR-SSCP)方法筛选c-kit基因外显子11突变病例。结果免疫组织化学检测结果:与高分化GIST相比,KIT蛋白在低分化GIST中表达强度较高(P<0.05)。Western-blot结果发现,与低侵袭危险度GIST比,KIT成熟蛋白在中高侵袭危险程度GIST中表达量较高(P<0.05)。c-kit基因外显子11突变率为52%(31/60),发生在女性、肿瘤最大径>5 cm、核分裂数>5/50 HPF及中高度侵袭危险性的GIST外显子11突变率较高(P<0.05)。在外显子11突变的GIST中成熟型KIT蛋白表达量较高(P<0.05)。结论 KIT成熟蛋白可能在GIST发生、发展中起重要作用,并且与GIST高度侵袭危险性的生物学行为相关;c-kit基因外显子11突变可能是GIST恶性生物学行为的指标。

Objective To study the relationship of c-kit gene’ s expression and mutation in the exon 11 to clinicopatho-logical features of gastrointestinal stromal tumor （ GIST） .Met hods A total of 60 GIST specimens （ including 15 fresh sam-ples） were obtained from the Second Affiliated Hospital of Dalian Medical University.Immunohistochemistry, Western-blot and RT-PCR were used to analyze c-kit gene expression, and PCR-SSCP was used to detecte c-kit exon 11 muta-tion.Results KIT protein expression detected by immunohistochemistry was higher in poorly differentiated GIST （ P 〈0.05）.The expression of KIT mature protein detected by western-blot was higher in the high invasion risk GIST （P〈0.05）.The frequency of c-kit gene exon 11mutation was 52 % （26/50）, mainly in the cases of women more than 60 years old, maximum tumor diameter〉5 cm, and the high invasion risk GIST （P〈0.05）.KIT mature protein expression is higher in GIST with exon 11 mutation （P〈0.05）.Conclu sions KIT mature protein expression might play an important role in the development of GIST and might associate with a high invasion risk c -kit gene exon 11 mutation might be an in-dicator of malignant biologic behavior in GIST.