程序性细胞死亡配体1在非小细胞肺癌手术切除标本及配对组织芯片中的表达分析

PD-L1 (SP142) Expression in Resected Specimens and Paired Tissue Microarrays Removed during Surgery for Non-Small Cell Lung Cancer

目的:观察非小细胞肺癌(non-small cell lung cancer,NSCLC)手术大标本及其配对微阵列组织标本(tissue microarrays,TMA)中程序性死亡受体1(programmed deathligand 1,PD-L1)表达状态,探索PD-L1表达的一致性及其临床意义。方法:采用免疫组化检测PD-L1(SP142)在129例NSCLC手术切除标本及配对TMA标本中肿瘤细胞(tumor cells,TC)及微环境浸润性免疫细胞(immune cells,IC)中的表达,分析PD-L1表达的一致性及其与临床病理特征之间的相关性。结果:PD-L1表达在手术标本和配对TMA测定之间经常表现出不一致,总体不一致率为41.9%,k值等于0.235(一致性差), IC的不一致率远高于TC。总体阴性标本(TC0/IC0)显示出中度的不一致性(49.6%),100例(77.5%)在手术标本和配对TMA中均被认为是TC0;然而,只有74例(57.4%)显示出IC0的一致性。有3例手术标本判读为IC3,但在配对TMA中未观察到IC3。与低评分组(TC1/IC1)相比,高PD-L1评分组(TC3/TC2/IC3/IC2)具有更好的一致性。不同组织学亚型不一致率之间存在趋势差异,肺鳞癌不一致率为33.3%,k值等于0.108;肺腺癌不一致率为48.5%,k值等于0.134(一致性差);PD-L1表达情况与患者总生存情况并无关联。结论:TMA中的PD-L1(SP142)表达低估了手术标本中的PD-L1状态。手术标本与配对TMA中发现了假阳性和假阴性结果。两种类型标本的不一致表达是肿瘤空间异质性的结果,可以对目前一些PD-L1免疫检查点抑制剂临床试验中的PD-L1表达与有效率不一致结果做出解释。使用目前临床可获取的病理小标本筛选PD-L1抑制剂优势人群还面临着较大的挑战。

Objective:To observe the expression status of programmed death-ligand 1(PD-L1,SP142)in large specimens removed during surgery for non-small cell lung cancer(NSCLC)and their paired tissue microarrays(TMA),and explore the consistency of PD-L1 expression and its clinical significance.Methods:PD-L1(SP142)immunohistochemistry assay was used to evaluate PD-L1(SP142)expression in tumor cells(TC)and tumor-infiltrating immune cells(IC)in resected surgical specimens and matched pairs of TMA in 129 patients with NSCLC,and analyze the consistency of PD-L1 expression and the correlation between the PD-L1 expression and its clinicopathological characteristics.Results:PD-L1 expression was frequently discordant between surgical specimens and matched TMA.The overall discordance rate was 41.9%,and k value was equal to 0.235(poor agreement).The discordance rate of PD-L1 expression in IC was much higher than that in TC.The overall negative specimens(TC0/IC0)showed a moderate discordance(49.6%).A hundred specimens(77.5%)were considered TC0 both in resected surgical specimens and paired TMA.However,only 74 IC0 specimens(57.4%)showed consistency in PD-L1 expression.Three resected specimens were considered IC3,but none IC3 was observed in paired TMA.Compared with the low PD-L1 group(TC1/IC1),the high PD-L1 group(TC3/TC2/IC3/IC2)showed better consistency.There was a difference in discordance rates among different histologic subtypes.The discordance rate of PD-L1 expression in lung squamous cell carcinoma was 33.3%,and k value was equal to 0.408;that in adenocarcinoma of lung was 48.5%,and k value was equal to 0.134;there was no association between PD-L1 expression and gender,tumor stage,smoking history,histology.Conclusion:PD-L1(SP142)expression in TMA specimens underestimate that in resected surgical specimens.False positive and false negative results are found in surgical specimens and paired TMA.The inconsistent expression in two types of specimens is the result of spatial heterogeneity of the tumor,which can explain the inconsistent results of PD-L1 expression and treatment efficiency in some current clinical trials of PD-1 and PD-L1 inhibitors.The use of current clinically available small pathological specimens to screen sensitive population of PD-L1 inhibitors is still facing great challenge.