PD-L1在肺大细胞神经内分泌癌中的表达和预后相关性及文献回顾

Association of PD-L1 Expression With Survival in Large Cell Neuroendocrine Lung Carcinoma and Literature Review

目的分析肺大细胞神经内分泌癌(large cell neuroendocrine lung carcinoma,LCNEC)中程序性死亡配体-1(programmed death ligand-1,PD-L1)的表达及其与预后的相关性,同时进行相关文献回顾。方法回顾性收集2016年1月至2021年7月期间于广东省人民医院病理科诊断为LCNEC并行PD-L1检测的患者42例,同时收集患者PD-L1检测结果、临床病理特征和预后数据,分析患者的PD-L1表达以及与临床病理特征和预后的相关性。通过PubMed检索LCNEC中PD-L1表达的相关研究报道。结果42例患者的中位年龄63岁,男性占85.7%,有吸烟史的患者占42.9%,手术切除标本占81%,标本中47.6%是纯大细胞神经内分泌癌,其余为复合性大细胞神经内分泌癌,复合成分为小细胞癌、腺癌或鳞癌。使用22C3或SP142抗体克隆行PD-L1检测,其中22C3抗体染色阳性率43.2%,SP142抗体阳性率60%,总体阳性率为45.2%。接受根治性手术的PD-L1阳性患者的无疾病生存期(disease-free survival,DFS)显著优于PD-L1阴性患者,然而整体的总生存期(overall survival,OS)未显示明显的差异。Cox回归分析显示PD-L1与DFS、OS均未见显著相关性。文献回顾11篇相关研究报道,共计713例病例,PD-L1表达的阳性率为10.4%~100%,免疫细胞的阳性率均高于肿瘤细胞,并且免疫细胞的阳性往往与更好的预后相关,而肿瘤细胞阳性在不同的研究中出现了相矛盾的预后相关性。结论LCNEC患者中部分表达PD-L1,并且PD-L1阳性患者具有更长的DFS。

Objective To ascertain the expression of programmed death ligand-1(PD-L1)on large cell neuroendocrine lung carcinoma(LCNEC),analysis its association with survival and review existing literatures.Methods Between January 2016 to July 2021,42 LCNEC patients diagnosed at Department of pathology,Guangdong Provincial People’s Hospital with PD-L1 detection were included.PD-L1 expression was analyzed by immunohistochemistry and the association of PD-L1 expression with clinicopathological characteristics and survival were performed.Previously published studies using PubMed search engine were reviewed.Results Forty-two cases of LCNECs were retrieved.Median age was63 years with male preponderance(85.7%).Nearly half of patients(42.9%)were smoker.81%of the specimens were from surgical resection.47.6%were diagnosed with pure LCNECs and the others were combined LCNECs with small cell lung cancer,adenocarcinoma and squamous carcinoma.Immunostaining of PD-L1 was performed using clone 22 C3 with the percentage positivity of 43.2%or SP142 with the percentage positivity of 60%and the overall percentage positivity was 45.2%.Patients with PD-L1 positive showed significantly longer disease-free survival(DFS)but not overall survival(OS)than those with PD-L1 negative,but in Cox regression analysis,PD-L1 was not associated with either DFS or OS.Eleven studies evaluating 713 LCNECs were reviewed.The percentage positivity varied from 10.4%~100%,which was higher in immune cells than that in tumor cells.Moreover,PD-L1 positivity in immune cells was associated with better prognosis,while the association of PD-L1 positivity in tumor cells with prognosis was still inconsistent.Conclusions PD-L1 positivity could be found in part of LCNECs,and DFS in patients with PD-L1 positive tends to be longer.