胃肠道间质瘤中c—kit和血小板衍生生长因子受体α基因的突变及其表达研究  

A study on the mutation and expression of c-kit and PDGFR-α gene in gastrointestinal stromal tumor

作　　者：郑松[1] 陈丽荣[1] 罗月球[2] 王海军[2] 程水珍[2] 朱永良[3] 周燕[2] 

机构地区：[1]浙江大学医学院附属第二医院肿瘤研究所,杭州310009 [2]浙江大学医学院病理科,杭州310009 [3]浙江大学医学院消化内科,杭州310009

出　　处：《中华普通外科杂志》2007年第8期574-578,共5页Chinese Journal of General Surgery

摘　　要：目的探讨c-kit和血小板衍生生长因子受体α（PDGFR—α）基因突变及其蛋白表达在胃肠道问质瘤（GIST）发病中的作用及与其临床病理、预后的关系。方法应用免疫组织化学EnvisionTM二步法检测了119例GIST中CD117和PDGFR-α蛋白的表达情况。用PCR扩增和基因测序的方法，检测50例GIST c—kit基因第9、11、13、17号外显子以及PDGFR—α基因第12、18号外显子的突变情况。结果本组119例GIST中CD-117的阳性表达率为87．4％，PDGFR-α的阳性表达率为65．5％。50例GIST中c—kit基因突变率为42％。突变均位于11号外显子近膜区的5’端第556～560密码子之间，即所谓的突变“热点”。50例GIST中PDGFR-α基因突变率为20％，最常见的突变为第18号外显子D842V点突变，2例为第12号外显子突变。c-kit基因突变主要见于CD117阳性的GIST，与GIST生物学侵袭行为无明显关系；而PDGFR-α基因突变主要见于CD117阴性的GIST，具高度侵袭危险性。未发现1例GIST有c—kit和PDGFR-α基因同时突变。结论PDGFR-α作为一种GIST特异而敏感的标记物，对一些CD117表达阴性的GIST的诊断及鉴别诊断具有重要的临床意义。作为GIST发病的两种分子机制，c—kit和PDGFR—α基因突变是相互排斥，不共存的。Objective To investigate the expression and mutation of c-kit and PDGFR-α gene and its relationship with clinical pathology and prognosis of patients of gastrointestinal stromal tumors. Methods In this study the expression of CD117 and PDGFR-α was studied by immunohistochemical method in 119 GIST cases. RT-PCR and DNA sequencing were used to evaluate the mutation of c-kit exons 9,11,13,17 and PDGFR-α exons 12,18 in 50 GIST cases. Results Of 119 GIST, 104（87. 4% ） were positive for CD- 117, 78（65.5% ） were positive for PDGFR-α. Overall, c-kit mutations were detected in 42% of GIST patients and all were exon 11 mutations. The types of c-kit exon 11 mutations were all heterogeneous and clustered between Codon 556-560,the classic ＂hot spot＂ at the 5＇end of exon 11. PDGFR-α mutations were found in 20% among the 50 cases. Of note, there were 5 PDGFR-α mutation cases in which the CD117 expression was negative. The commonest type of mutation was the point mutation of D842V of exonl8. Mutations of exon 12 were found in 2 GIST. c-kit oncogenic mutations were more likely seen in CDl17 positive GIST and had no obvious relationship with biological behavior of GIST. PDGFR-α oncogenic mutations were more likely seen in CDll7 negative GIST and had an unfavorable clinical course. In this study, we have not found concomitant c-kit and PDGFR-α gene mutations in a same individual GIST case. Conclusion As a sensitive and specific marker of GIST, PDGFR-α can be used in combination with CD117 for the diagnosis and differential diagnosis of GIST especially in those cases in which the tumor does not express CD-117.

关 键 词：胃肠道间质肿瘤 原癌基因蛋白质C-KIT 受体 血小板源生长因子α 突变 

分 类 号：R686[医药卫生—骨科学]