摘要
目的分析胃肠间质瘤(GISTs)中DOG1、CD117与类胰岛素生长因子1受体(IGF1R)的表达以及c-KIT和PDGFRA基因突变情况,并探讨它们与GISTs临床病理特征的关系及意义。方法免疫组化检测98例GISTs中DOG1、CD117和IGF1R的表达情况及40例非GISTs间叶源性肿瘤中DOG1和CD117的表达情况。基质辅助激光解析电离飞行时间质谱法检测77例GISTs中c-KIT和PDGFRA基因突变情况。结果 GISTs中DOG1、CD117及IGF1R的阳性表达率分别为92.9%、95.9%和6.1%,非GISTs间叶源性肿瘤中DOG1和CD117阳性表达率分别为10.0%和17.5%,两者中DOG1和CD117阳性表达率的差异有统计学意义(P<0.001)。GISTs中DOG1的表达与肿瘤大小及危险度有关,CD117表达与肿瘤部位及组织学类型有关,IGF1R表达与临床病理特征无关。77例GISTs中c-KIT、PDGFRA基因的突变率分别为64.9%和22.1%,两个基因分别以外显子11(54.0%)和外显子12(16.9%)突变最多见。c-KIT、PDGFRA基因突变仅与肿瘤部位有关(P=0.001,P=0.002)。CD117、DOG1的表达与c-KIT和PDGFRA基因是否突变无关,而野生型及突变型(存在c-KIT或PDGFRA基因突变)GISTs中IGF1R表达差异有统计学意义。结论联合检测DOG1、CD117可以提高诊断GISTs的准确性,尤其是CD117表达,两者均与临床病理特征有关。IGF1R可能是野生型GISTs特异性的免疫组化指标和潜在治疗靶点。将肿瘤原发部位与基因突变检测结果相结合,对预测GISTs患者应用酪氨酸激酶抑制剂的疗效以及预后更具指导价值。
Objective To investigate expressions of discovered on GIST-1 （ DOG1 ） , CD117 and insulin-like growth factor 1 receptor （IGF1R） , and the mutation status of c-KIT and PDGFRA gene in gastrointestinal stromal tumors （GISTs）, as well as the relations between them and elinicopathologic features of GISTs. Methods The expressions of DOG1, CD117 and IGF1R were detected by immunohistoehemistry in 98 GISTs and 40 non-GISTs. Mutations of c-KIT and PDGFRA were analyzed using a matrix-assisted laser desorption/ionization-time of flight （MALDI-TOF） mass spectrometer. Results The positive expression rates of DOG1, CD117 and IGF1R in GISTs were 92.9% , 95.9% and 6. 1% , respectively. And in non-GISTs, the positive rates of DOG1 and CD117 were 10. 0% and 17.5% , lower than those in GISTs（P 〈0. 001 ）. The expression of DOG1 was correlated with tumor size and risk degree. For CD117, its expression was related to tumor location and histological types. IGF1R was not significantly associated with clinieopath- ologic features. Of 77 GISTs, mutation rates of c-KIT and PDGFRA were 64.9% and 22. 1% , and the most common mutational sites were exon 11 （ 54.0% ） and 12 （ 16.9% ） respectively. The mutation rates of PDGFRA and c-KIT were only related to tumor location（ P =0. 001, P =0. 002）. Expressions of CDll7 and DOG1 were not related to mutations of c-KIT or PDGFRA gene. But IGF1R＇ s expression was significantly different between wild-type and mutated GISTs. Conclusion Detection of both DOG1 and CD117 can raise the diagnostic rate of GISTs, especially for those who has negative expression of CD117 and the results can help analyze clinicopathologic features of GISTs comprehensively. Our results suggest that IGF1R is a special marker and potential therapeutic target for wild-type GISTs. There will be more useful to analyze response to tyrosine kinase inhibitors and prognosis of GISTs with gene mutation analysis and tumor locations.
出处
《临床肿瘤学杂志》
CAS
2012年第10期874-879,共6页
Chinese Clinical Oncology
基金
广东省自然科学基金资助项目(9151051501000016)
