老年非小细胞肺癌患者中EGFR突变、PD-L1、Ki-67表达及其与临床特征的相关性

EGFR mutation,expression of PD-L1/Ki-67 and their correlation with clinical features in elderly NSCLC patients

目的分析老年非小细胞肺癌(NSCLC)患者中血管内皮生长因子受体(EGFR)突变、程序性死亡配体1(PD-L1)、细胞增殖相关抗原(Ki-67)表达及其与患者性别、组织学类型、TNM分期等临床参数间的相关性。方法收集2020年1月至12月在复旦大学附属华东医院就诊的340例老年NSCLC患者组织标本,其中男性195例,女性145例,年龄(68.9±6.0)岁。按性别、组织学类型及TNM分期等临床参数对患者进行分组。采用超级突变扩增阻滞系统(Super-ARMS)方法及免疫组化方法检测老年NSCLC患者中EGFR突变、PD-L1及Ki-67的表达情况,对EGFR突变、PD-L1及Ki-67的表达与临床参数间的相关性进行统计学分析,采用Pearson相关分析EGFR突变与PD-L1及Ki-67表达间的相关性。结果在老年NSCLC患者组织标本中,EGFR突变阳性率为48.53%(165/340),以L858R和19del突变最为常见,分别为56.36%(93/165),30.30%(50/165)。其中EGFR的突变率在女性、肺腺癌、高分化、Ⅰ+Ⅱ分期患者中较高,分别为65.52%(95/145)、53.77%(164/305)、56.75%(143/252)、52.53%(135/257)。此外,PD-L1表达阳性率在老年肺非腺癌患者和中/低分化腺癌中较高,分别为37.14%(13/35),24.53%(13/53)。PD-L1表达阴性率在Ⅰ+Ⅱ期、淋巴结未转移及Ki-67弱阳性老年NSCLC患者中较高,分别为89.11%(229/257)、87.63%(248/283)、94.71%(197/208)。相关性分析显示,EGFR突变与PD-L1及Ki-67的表达呈负相关(PD-L1:r=-0.22,P<0.001;Ki-67:r=-0.32,P<0.001)。结论老年NSCLC患者中EGFR突变与PD-L1及Ki-67表达呈负相关,EGFR突变与PD-L1表达联合检测对指导老年NSCLC患者的靶向用药和免疫治疗具有重要的意义。

Objective To investigate the mutation of epidermal growth factor receptor(EGFR),the expression of programmed death ligand 1(PD-L1),cell proliferation-associated antigen(Ki-67)in elderly patients with non-small cell lung cancer(NSCLC),and their correlation with clinical feature such as gender,histological type and TNM stage.Methods The tissue samples of 340 elderly NSCLC patients with definite histopathological diagnosis were collected from January 2020 to December 2020 in Huadong Hospital Affiliated to Fudan University,including 195 males and 145 females,age between 68.9±6.0 years.Patients were grouped according to clinical features such as gender,histological type and TNM stage.The expression of EGFR mutation,PD-L1 and Ki-67 were detected by Super-ARMS and immunohistochemistry.The correlation between tnem and clinical features was statistically analyzed,and the correlation between EGFR mutation and PD-L1/Ki-67 expression was further analyzed separately.Results In elderly NSCLC patients′tissues,the positive rate of EGFR mutation was 48.53%(165/340).L858R and 19del mutations were the most common types,which were 56.36%(93/165),30.30%(50/165)respectively.The mutation rate of EGFR was higher in women,lung adenocarcinoma,well-differentiated,and low-stage patients,which were 65.52%(95/145),53.77%(164/305),56.75%(143/252),52.53%(135/257)respectively.In addition,the positive rate of PD-L1 expression was higher in elderly patients with non-adenocarcinoma lung cancer and poorly differentiated adenocarcinoma,which were 37.14%(13/35),24.53%(13/53)respectively.The negative rate of PD-L1 expression was higher in elderly patients with NSCLC in stageⅠ+Ⅱ,no lymph node metastasis and weakly positive Ki-67,which were 89.11%(229/257),87.63%(248/283),94.71%(197/208)respectively.Correlation analysis showed that EGFR mutation was negatively correlated with the expression of PD-L1 and Ki-67(PD-L1:r=-0.22,P<0.001;Ki-67:r=-0.32,P<0.001).Conclusion There is a negatively correlation between EGFR mutation and the expression of PD-L1 and Ki-67 in elderly NSCLC,suggesting that the combined detection of EGFR mutation and PD-L1 expression could provide the basis for precise targeted therapy for elderly NSCLC patients.