KRAS、BRAF基因突变的结直肠癌患者临床病理特征分析  

Clinicopathological characteristics of colorectal cancer in patients with KRAS and BRAF mutations

作　　者：刘威 王菲 杜洪 缪娜波 李旺林[1,2] 曹杰 Liu Wei;Wang Fei;Du Hong;Miao Nabo;Li Wanglin;Cao Jie(Department of Colorectal and Anal Surgery,Guangzhou Digestive Disease Center,Guangzhou First People s Hospital,Guangzhou Medical University,Guangzhou 510180;Guangzhou First People s Hospital,Second Affiliated Hospital of South China University of Technology,South China University of Technology Digestive Diseases Institute,Guangzhou 510180;Department of Pathology,Guangzhou First People s Hospital,Second Affiliated Hospital of South China University of Technology,Guangzhou 510180,China)

机构地区：[1]广州医科大学附属广州市第一人民医院,广州消化疾病中心,结直肠肛门外科,广东广州510180 [2]广州市第一人民医院,华南理工大学附属第二医院,华南理工大学消化疾病研究所,广东广州510180 [3]广州市第一人民医院,华南理工大学附属第二医院病理科,广东广州510180

出　　处：《广州医科大学学报》2021年第4期13-18,共6页Academic Journal of Guangzhou Medical University

基　　金：国家自然科学基金(81871943);广东省自然科学基金(2017A030311035)。

摘　　要：目的:探讨结直肠癌患者KRAS、BRAF基因突变情况及其临床病理特征。方法:收集广州市第一人民医院2017年7月至2020年12月手术切除的724例结直肠癌患者的肿瘤标本,运用突变阻滞扩增系统PCR检测KRAS基因第2、3、4号外显子及BRAF基因第15号外显子第600位密码子的突变情况,运用免疫组化检测错配修复蛋白MLH1、PMS2、MSH2、MSH6及Ki-67、P53、CD34、D2-40、S-100等基因表达情况,分析KRAS、BRAF基因突变与患者临床病理特征的关系。结果:KRAS基因总突变率为30.4%(220/724),其中第2号外显子突变率最高,为21.9%(200/724);BRAF基因第15号外显子第600位密码子突变率为4.0%(29/724)。与野生型结直肠癌相比,KRAS基因突变的结直肠癌多发生于男性,浸润型比例更高(P<0.05);BRAF基因突变的结直肠癌多发生于女性,右半结肠、错配修复功能缺陷、浸润型比例更高,且恶性程度更高(P<0.05)。与KRAS基因突变的结直肠癌相比,BRAF基因突变的结直肠癌多发生于右半结肠,错配修复功能缺陷比例及恶性程度更高(P<0.05)。结论:KRAS及BRAF基因突变的结直肠癌在临床病理特征上存在差异,检测KRAS、BRAF基因状态可为结直肠癌患者的治疗提供理论依据。Objective:To investigate the KRAS and BRAF mutations and the clinicopathological characteristics in patients with colorectal cancer.Methods:Tumor specimens were collected from 724 patients with colorectal cancer who underwent surgical resection between July 2017 and December 2020 in Guangzhou First People s Hospital.Amplification refractory mutation system PCR was used to detect the mutations of the exons 2,3,and 4 in KRAS and of exon 15 codon 600 in BRAF.Immunohistochemistry was used to detect the expression of several mismatch repair proteins(MLH1,PMS2 MSH2 and MSH6),Ki-67,P53,CD34,D2-40,and S-100.The relationship between KRAS and BRAF gene mutations and clinical pathological characteristics in the patients was analyzed.Results:The total rate of KRAS mutation was 30.4%(220/724),and the mutation was most commonly in exon 2[21.9%(200/724)].The mutation rate of BRAF exon 15 codon 600 was 4.0%(29/724).Compared with wild-type colorectal cancers,colorectal cancers with KRAS mutations mostly occurred in men,and were with a higher proportion of invasiveness(P<0.05).Colorectal cancers with BRAF mutations mostly occurred in women,and were more frequently seen in the right hemicolon and more with mismatch repair defects,higher invasiveness and malignancy(P<0.05).Compared with colorectal cancer with KRAS mutation,colorectal cancer with BRAF mutation mostly occurred in the right colon,and were more with mismatch repair defects and higher malignancy(P<0.05).Conclusion:KRAS and BRAF mutants of colorectal cancers differ in clinicopathological characteristics.Detection of KRAS and BRAF mutations may offer evidence for treatment of colorectal cancer in the patients.

关 键 词：结直肠癌 KRAS BRAF 基因突变 临床病理特征 

分 类 号：R576[医药卫生—消化系统]