179例胃间质瘤临床病理特征及基因突变类型分析

Characteristics of Clinicopathology and Genotype in 179 Cases with Gastrointestinal Stromal Tumor

中文关键词:  胃肠间质瘤 临床病理特征 基因突变 基因分型

英文关键词:Gastrointestinal stromal tumor Clinicopathology Mutation Genotype

中文摘要:

      目的 分析胃肠间质瘤（GIST）患者临床病理特征、基因突变类型和突变位点特征。方法 回顾性收集2009年9月至2015年2月四川大学华西医院收治的179例行基因检测的GIST患者并分析其各临床病理资料的特征。结果 所有患者中，肿瘤原发于胃88例（49.2%），小肠70例（39.1%），结直肠7例（3.9%），其它部位14例（7.8%）；其中CD117、CD34、DOG-1阳性率分别为为94.4%、74.9%、93.3%。GIST患者基因突变c-kit突变最为常见，共151例（84.4%），其次为PDGFRα突变8例（4.5%），野生型20例（11.2%）。c-kit突变中，外显子11以缺失突变、点突变及缺失+插入突变为主（92.2%）；外显子9突变共有6例（30%） A502-Y503复制突变及14例（70%）Y403-F504插入突变；外显子13突变为1例K642Q点突变，外显子17突变为2例N822K点突变。在6例PDGFRα外显子18突变患者中，分别有5例和1例发生点突变和缺失突变，点突变中3例为D842V突变。在GIST的基因分型中，PDGFRα突变患者DOG-1阳性率低于c-kit突变及野生型患者（ P=0.007），而在c-kit各突变类型中，点突变患者CD34患者阳性率低于其它突变类型（ P<0.001），点突变和插入突变患者中高危患者比例低于缺失突变和缺失+插入突变（ P=0.006）。结论 胃和小肠是GIST最常见的发病部位；c-kit外显子11是GIST最常见的基因突变类型；GIST基因突变率高且突变类型多样，不同患者需提供个体化治疗。

英文摘要:

      Objective To analyze the characteristics of the clinicopathology and genotypes in patients with gastrointestinal stromal tumor (GIST). Methods The clinicopathological and genotypic data of 179 patients with GIST, who underwent treatment and genetic testing in the Hostital of West China from September 2009 to February 2009 were collected retrospectively. Results The tumor sites of the cases were located in stomach (88 cases, 49.2%), small intestine (70 cases, 39.1%), colorectum (7 cases, 3.9%) and the other sites (14 cases, 7.8%) respectively. 94.4%, 74.9% and 93.3% of GIST patients were positive for CD117, CD34 and DOG-1 immunophenotypes respectively.c-kit and PDGFRαmutations were found in 151 cases (84.4%) and 8 cases (4.5%) except for the wild types of the rest 20 cases (11.2%). Among all thec-kit mutation, 92.2% mutation types in exon 11 were deletion mutation, point mutation and hybrid mutations, and in exon 9 the mutation types were just involving A502_Y503dup (n=6) and Y403_F504ins (n=14), while the mutation type were K642Q in exon 13 (n=1) and N822K in 17 (n=2). There were 6 patients with the mutation types of PDGFRαin exon 18, and 3 of them were type of D842V. In the GIST genotyping, DOG-1 positive rate in PDGFRαmutation patients were significantly lower than that inc-kit mutation and wild type patients ( P=0.007). In the various type ofc-kit mutations, the positive rate of CD34 in point mutation patients were significantly lower than that in other mutation types ( P<0.001). The rate of high-risk patients in point mutation and insertion mutation patients were lower than that in deletion mutation and deletion + insertion mutation patients ( P=0.006). Conclusion The most common localizaions of GISTs are the stomach and small intestine. The most frequent mutation type of GIST isc-kit exon 11. The individualized treatment is required for GIST patients because its high mutation rate and types.