HER2基因20号外显子插入突变非小细胞肺癌患者临床病理学特征及治疗效果随访  

Clinicopathological characteristics and follow-up on therapeutic effect of non-small cell lung cancer patients with HER2 exon 20insertion mutations

作　　者：孙文佳 岳君秋 王满香 SUN Wenjia;YUE Junqiu;WANG Manxiang(Department of Pathology,Hubei Cancer Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430070,China)

机构地区：[1]华中科技大学同济医学院附属湖北肿瘤医院病理科,湖北武汉430070

出　　处：《中华肿瘤防治杂志》2023年第17期1029-1033,共5页Chinese Journal of Cancer Prevention and Treatment

基　　金：武汉中青年医学骨干人才培养工程项目(武卫生计生[2014]41号)。

摘　　要：目的探讨人表皮生长因子受体2(HER2)基因20号外显子插入(ex20ins)突变非小细胞肺癌(NSCLC)患者的临床病理学特征、治疗及随访。方法收集2022-01-01-12-31华中科技大学同济医学院附属湖北肿瘤医院病理科确诊的472例NSCLC患者标本。采用荧光定量PCR法检测472例NSCLC中HER2基因状态,采用χ^(2)检验或连续校正的χ^(2)检验分析HER2 ex20ins突变与临床病理学特征的关系。结果472例患者中检测出HER2 ex20ins突变12例(2.54%),其中男7例,女5例;年龄35~65岁,中位年龄58.5岁;病理类型均为腺癌,其中中分化5例,低分化7例;肿瘤分期:Ⅰ期4例,Ⅲ期2例,Ⅳ期6例。≤65岁患者HER2 ex20ins的突变率为4.41%(12/272),>65岁患者为0(0/200),差异有统计学意义,χ^(2)=9.054,P=0.003;无吸烟史患者HER2 ex20ins的突变率为3.83%(10/261),有吸烟史患者为0.95%(2/211),差异有统计学意义,χ^(2)=3.915,P=0.048;HER2 ex20ins突变与患者性别(χ^(2)=0.000,P=1.000)、肿瘤分期(χ^(2)=0.773,P=0.379)、病理类型(χ^(2)=1.429,P=0.232)和腺癌分化程度(χ^(2)=0.208,P=0.648)差异均无统计学意义;HER2 ex20ins在原发灶与转移灶中的阳性率分别为2.72%(9/331)和2.13%(3/141),差异无统计学意义,χ^(2)=0.003,P=0.957。随访12例HER2 ex20ins突变NSCLC患者,中位随访时间8个月(3~13个月),4例Ⅰ期患者术后均无复发;其余8例均带瘤生存。2例晚期患者行HER2酪氨酸激酶抑制剂(TKI)治疗,使用阿法替尼的患者无进展生存期(PFS)为6个月,使用吡咯替尼的患者PFS为8个月。结论NSCLC中HER2 ex20ins突变与患者年龄、是否吸烟相关。靶向治疗对部分患者有效,但需要大样本临床研究进一步证实TKI对HER2 ex20ins突变NSCLC患者的疗效。Objective To investigate the clinicopathological features,treatment and follow-up of non-small cell lung cancer(NSCLC)patients with human epidermal growth factor-2(HER2)gene exon 20insertion(ex20ins)mutation.Methods We collected 472specimens of NSCLC patients diagnosed by Department of Pathology,Hubei Cancer Hospital,Tongji Medical College,Huazhong University of Science and Technology from January 1to December 31,2022.The status of HER2gene was detected by real-time quantitative PCR,and the correlation between HER2ex20ins mutation and clinicopathological features was analyzed byχ^(2) test orχ^(2) test with continuous correction.Results We found 12(2.54%)HER2 ex20ins mutations in 472patients,including 7males and 5females.The median age was 58.5(from 35to 65).All of them were adenocarcinomas,5were moderately differentiated and 7poorly differentiated.Four cases were stageⅠ,2 were stageⅢ,and 6were stageⅣ.The mutation rate of HER2ex20ins in patients≤65years was 4.41%(12/272),and that in patients>65years was 0(0/200),the difference was statistically significant(χ^(2)=9.054,P=0.003).The mutation rate of patients without smoking history was 3.83%(10/261),and that of patients with smoking history was 0.95%(2/211),the difference was statistically significant(χ^(2)=3.915,P=0.048).There was no statistical difference in gender(χ^(2)=0.000,P=1.000),tumor stage(χ^(2)=0.773,P=0.379),pathological type(χ^(2)=1.429,P=0.232),and degree of adenocarcinoma differentiation(χ^(2)=0.208,P=0.648).The positive rates of HER2ex20ins in primary and metastatic lesions were 2.72%(9/331)and 2.13%(3/141),respectively,with no significant difference(χ^(2)=0.003,P=0.957).Twelve patients were followed up for a median time of 8months(3to 13months).Four patients in stageⅠsurvived without relapse after surgical resection,the other 8patients survived with disease.Two advanced patients were treated with HER2tyrosine kinase inhibitor(TKI).The progression-free survival of patient using alfatinib was 6months,and that was 8months using pyrot

关 键 词：非小细胞肺癌 人表皮生长因子受体2 基因突变 临床病理特征 

分 类 号：R734.2[医药卫生—肿瘤]