浸润性肺腺癌组织学亚型与驱动基因状态的相关性研究  

Correlation between histological subtype and driver gene status of pulmonary adenocarcinoma

作　　者：周兵[1] 王洁[1] 彭丽姿 张剑锋 ZHOU Bing;LIU Haoru;PENG Lizi;ZHANG Jianfeng(The First People's Hospital of Jiujiang,Jiujiang 332000,China;Jiangxi Cancer Hospital,Nanchang 332000,China)

机构地区：[1]九江市第一人民医院,江西九江332000 [2]江西省肿瘤医院,江西南昌330029

出　　处：《临床医药实践》2021年第11期810-816,共7页Proceeding of Clinical Medicine

基　　金：江西省卫生健康委员会科技计划资助项目(项目编号:202120056)。

摘　　要：目的:探讨浸润性肺腺癌组织学亚型与驱动基因状态的相关性,为临床预后评估和基因检测筛选提供新的思路。方法:收集浸润性肺腺癌手术标本87例,依据肺腺癌国际多学科标准(IASLC/ATS/ERS)对组织学亚型进行分类;高通量二代测序(NGS)检测驱动基因突变状态,并结合临床特征资料分析两者的相关性。结果:87例浸润性腺癌中腺泡为主亚型,占51.7%(45/87),与贴壁生长为主型[9.2%(8/87)]和微乳头状为主型的亚型[8.1%(7/87)]比较,差异有统计学意义(χ^(2)=19.645,P<0.001)。87例标本中共检出7种驱动基因,共计68例突变,总突变率为78.2%。表皮生长因子受体(EGFR)突变率为48.3%(42/87),与女性患者(χ^(2)=6.034,P=0.014)、无吸烟史(χ^(2)=4.949,P=0.026)、临床分期Ⅲ~Ⅳ存在相关性(χ^(2)=4.158,P=0.041);同时EGFR在具有贴壁生长和微乳头状组织学亚型中突变率相较于其他类型显著增高(χ^(2)=7.305,P=0.007)。鼠类肉瘤病毒癌基因(KRAS)突变率为11.5%(10/87),与吸烟史存在相关性(χ^(2)=4.249,P=0.039),但与组织学亚型无关。间变性淋巴瘤激酶(ALK)突变率为9.2%(8/87),与女性(χ^(2)=4.774,P=0.029)、年龄<60岁(χ^(2)=5.056,P=0.024)存在相关性;同时,ALK在具有黏液实体状组织学亚型的突变率与其他类型比较,差异无统计学意义(χ^(2)=4.991,P=0.026)。肝细胞生长因子(c-MET)突变率5.7%(5/87),与临床病理特征无明确相关性,但微乳头为主型的突变率与其他类型比较,差异有统计学意义(Fisher精确概率,P=0.042)。鼠类肉瘤病毒癌基因同源物基因(BRAF)突变率2.3%(2/87)、酪氨酸激酶受体2(ERBB2)和肉瘤致癌因子-受体酪氨酸激酶(ROS1)基因各突变1例,未发现RET原癌基因(RET)突变,由于以上基因突变少,暂未发现与临床特征及组织学亚型存在相关性。结论:EGFR,KRAS,ALK和c-MET基因突变与临床特征存在一定的相关性,且EGFR在贴壁生长和微乳头状组织学亚型中突变率更高,ALK突变Objective:To investigate the correlation between histological subtype and driving gene status of pulmonary adenocarcinoma.It provides a new idea for clinical prognosis evaluation and gene screening.Methods:All 87 cases of pulmonary adenocarcinoma were collected,classified of histological subtypes according to the IASLC/ATS/ERS for pulmonary adenocarcinoma.High-throughput next-generation sequencing(NGS)to detect the status of driver gene mutation,and the correlation between histological subtype and driver gene status was analyzed.Results:In 87 cases of pulmonary adenocarcinoma,the acinar patterns was 51.7%(45/87),compared with 9.2%(8/87)of solid pattern predominant with mucin secretion and 8.1%(7/87)of micropapillary patterns(χ^(2)=19.645,P<0.001).A total of 68 mutations of 7 driving genes were detected in 87 specimens.The total mutation rate is 78.2%.Epithelial growth factor receptor(EGFR)mutation rate was 48.3%(42/87),the mutation rate was higher in female(χ^(2)=6.034,P=0.014)、non-smokers(χ^(2)=4.949,P=0.026)and clinical stageⅢ~Ⅳ(χ^(2)=4.158,P=0.041).EGFR mutation was mostly caused by Lepidic and micropapillary predominant was significantly higher than other subtypes(χ^(2)=7.305,P=0.007).The mutation rate of kirsten rat sarcoma(KRAS)was 11.5%(10/87),which is correlated with a history of smoking(χ^(2)=4.249,P=0.039),but not related to histological subtypes.The mutation rate of anaplastic lymphoma kinase(ALK)was 9.2%(8/87),the mutation rate was higher in female(χ^(2)=4.774,P=0.029)and<60 years(χ^(2)=5.056,P=0.024).ALK was predominant in solid pattern with mucin secretion(χ^(2)=4.991,P=0.026).The mutation rate of mesenchymal-epithelial transition factor(c-MET)was 5.7%(5/87).There is no clear correlation with clinicopathological features,However,there was statistically difference in the mutation rate of microemulsion(Fisher exact probability,P=0.042).The mutation rate of V-rafmurine sarcoma viral(BRAF)was 2.3%(2/87).Human epidermal growth factor receptor 2(ERBB2)and C-ros oncogene 1(ROS1)gene was 1 ca

关 键 词：肺腺癌 组织学亚型 驱动基因 

分 类 号：R446.8[医药卫生—诊断学]