胃癌组织中HER-2基因扩增和K-ras基因突变的关系

Relations between HER-2 gene amplification and K-ras gene mutation in gastric cancer tissues

目的探讨胃癌组织中HER-2蛋白表达和基因扩增与K-ras基因突变的关系及其意义。方法采用免疫组化、FISH和焦磷酸测序技术对67例胃癌组织中HER-2蛋白表达、HER-2基因扩增与K-ras基因的突变率进行了检测。结果 HER-2蛋白阳性率为40.3%(27/67),其中HER-2蛋白3+者9.0%(6/67),HER-2蛋白2+者13.4%(9/67),HER-2蛋白1+者17.9%(12/67)。FISH检测HER-2基因扩增率为18.5%(5/27),HER-2基因拷贝数增加和基因扩增者共48.1%(13/27)。K-ras基因突变定量检测为7.5%(5/67),均为K-ras基因第12密码子突变,其中低于10%低丰度突变2例,高于10%高丰度突变3例(突变数值分别为:17、29、30)。除1例为GGT→GAT突变型外,其它均为GGT→GTT突变型。本组K-ras基因突变5例中除1例既有K-ras基因突变,又有HER-2基因扩增,另外4例HER-2基因均无扩增。结论检测胃癌中HER-2扩增时选用抗肿瘤药物治疗的靶点曲妥珠单抗,同时可选用K-ras基因突变的抗肿瘤药物治疗的靶点西妥昔单抗;联合检测胃癌组织中HER-2基因扩增和K-ras基因突变为靶向抗肿瘤药物治疗过程中受益提供参考指标。

Purpose To investigate the relationship between HER-2 expression and gene amplification and K-ras mutation in gastric cancer tissues and its significance. Methods HER-2 protein expression, HER-2 gene amplification and K-ras mutation rate of 67 ca- ses of gastric cancer were expressed by immunohistochemistry （ IHC）, fluorescence in situ hybridization （FISH） and gene sequencing technology. Results The expression of HER-2 protein was 40.3% （27/67）, of which HER-2 positive 3 ＋ was 9% （6/67）, HER- 2 protein 2 ＋ 13.4% （9/67） and HER-2 protein 1 ＋ 17. 9% （12/67）. The HER-2 gene amplification rate ofFISH was 18.5% （5/ 27）, the increased copy number of HER-2 gene and the gene amplification were 48.1% （13/27）. K-ras gene mutation rate was 7.5% （5/67）, in which all occurred in codon 12 mutations, the K-ras mutation was less than 10% of low abundance mutations in 2 cases, more than 10% of the high abundance mutation in 3 cases （mutant numbers were 17, 29, 30, respectively）. Except for the mutation of GAT 〉 GGT, the other mutations were GGT 〉 GTT except for 1 case. The mutations of K-ras gene in 5 cases were not only of K-ras gene mutations, but also HER-2 gene amplification, and the other 4 cases of HER-2 gene were not amplified. Conclu- sion HER-2 amplification can be used as target of antitumor drug trastuzumab. At the same time K-ras gene mutation can be selected as another target for antitumor drug cetuximab. Combined detection of HER-2 gene amplification and K-ras gene mutation provide refer- ence markers for better targeting therapy that may be benefit to patients.