肺腺癌常见驱动基因变异与临床病理分型的相关性  

Correlation between common driver gene variations and clinicopathological typing in lung adenocarcinoma

作　　者：马夏林 贾若楠 韩凯 张云香[1] Ma Xialin;Jia Ruonan;Han Kai;Zhang Yunxiang(Center of Precision Pathologic Diagnosis,the First Affiliated Hospital of Shandong Second Medical University(Weifang People′s Hospital),Weifang 261041,China;Department of Basic Medicine,Shandong Second Medical University,Weifang 261053,China)

机构地区：[1]山东第二医科大学第一附属医院、潍坊市人民医院精准病理诊断中心,潍坊261041 [2]山东第二医科大学基础医学院,潍坊261053

出　　处：《中华病理学杂志》2024年第6期578-584,共7页Chinese Journal of Pathology

基　　金：山东省自然科学基金面上项目(ZR2023MH064);山东省医药卫生科技项目(202302061370);潍坊市科技发展计划项目(2022YX001);潍坊市软科学研究计划项目(2021RKX137)。

摘　　要：目的探讨原发性肺腺癌常见驱动基因变异与患者临床特征及病理分型之间的相关性。方法回顾性分析山东省潍坊市人民医院2015年1月至2021年12月首次确诊为原发性肺腺癌的病例4995例。因1983例标本病理分型评估局限,3012例进行了驱动基因变异与病理分型相关性分析,分别分析其与浸润性非黏液性腺癌、浸润性黏液腺癌等病理分型的相关性及与形态学高、中、低分化的相关性。采用二代测序检测患者肿瘤组织样本表皮生长因子受体(EGFR)、KRAS、间变性淋巴瘤激酶(ALK)、RET、ROS1、MET、HER2、BRAF驱动基因变异情况。结果患者男性2384例,女性2611例。在临床特征分析中,肺腺癌EGFR、ALK变异多见于≥60岁女性患者,EGFR在临床分期Ⅰ期突变率(25.80%)高于其他分期突变率(P<0.05)。KRAS突变多见于≥60岁吸烟男性患者,HER2突变多见于<60岁患者,RET融合多见于非吸烟患者(均P<0.05)。未发现ROS1、MET、BRAF基因变异与临床特征的相关性(P>0.05)。在病理分型分析中,相较于其他7个基因,1899例腺泡型腺癌中EGFR突变率最高(67.30%),其中在浸润性黏液腺癌及浸润性非黏液性腺癌中外显子21 L858R、外显子19缺失为主要突变位点,在微乳头型中外显子20 T790M的突变率(11.63%)较高。在浸润性黏液腺癌中,KRAS总突变率检测最高(43.80%),其中外显子2 G12D、外显子2 G12V在腺泡型、实体型和浸润性黏液腺癌中突变率组间比较差异有统计学意义(P<0.05)。KRAS各位点在低分化组比高~中分化组突变率高(P<0.05)。HER2突变多发生在浸润性非黏液性腺癌的腺泡型、乳头型和微浸润性腺癌中。BRAF在微浸润性腺癌中突变率高于其他类型(P<0.05)。结论原发性肺腺癌中EGFR、ALK、KRAS、HER2、RET变异与患者年龄、吸烟史及临床分期有关,且在不同的病理亚型中驱动基因变异有所不同。在浸润性非黏液腺癌中以EGFR突变为主,在浸润性�Objective To correlate the common driver gene variations in primary lung adenocarcinoma with their clinical characteristics and histopathological subtypes.Methods There were 4995 cases of primary lung adenocarcinoma diagnosed at Weifang People′s Hospital of Shandong Province from January 2015 to December 2021 which were retrospectively analyzed.Among them 1983 cases were evaluated for their histopathological subtype;3012 were analyzed for the correlation of their histopathological subtypes and corresponding driver gene variations,including invasive non-mucinous adenocarcinoma(INMA)and invasive mucinous adenocarcinoma(IMA),and morphologically,poorly-differentiated,moderately-differentiated and well-differentiated adenocarcinomas.Next-generation sequencing was used to detect variations in EGFR,KRAS,ALK,RET,ROS1,MET,HER2,or BRAF driver genes.Results There were 2384 males and 2611 females.EGFR and ALK variations were more commonly found in female patients aged 60 years or older,with EGFR mutation rate in clinical stageⅠ(25.80%)significantly higher than in other stages(P<0.05).KRAS mutations were more commonly detected in male smokers aged 60 years or older,HER2 mutations were more commonly in patients younger than 60 years,and RET mutations were more commonly in non-smokers(all P<0.05).No correlation was found between ROS1,MET,and BRAF gene variations and their clinical characteristics(P>0.05).For the histopathological subtypes,among the 1899 cases of acinar adenocarcinoma,EGFR mutation rate was the highest(67.30%)compared to the other genes.Exon 21 L858R and exon 19 del were the main mutation sites in IMA and INMA,with a higher mutation rate at exon 20 T790M(11.63%)in micropapillary adenocarcinoma.In IMA,KRAS had the highest overall mutation rate(43.80%),with statistically significant difference in mutation rates of exon 2 G12D and exon 2 G12V in acinar adenocarcinoma,solid,and IMA(P<0.05).KRAS mutation at various sites were higher in poorly differentiated groups compared to moderately-and well-differentiated gr

关 键 词：肺肿瘤 腺癌 DNA突变分析 受体 表皮生长因子 

分 类 号：R734.2[医药卫生—肿瘤]