回顾性队列研究 NSCLC 患者中 PD-L1 阳性率、分子相关性和临床结局：欧洲胸部肿瘤平台（ETOP）Lungscape 项目的结果。
A retrospective cohort study of PD-L1 prevalence, molecular associations and clinical outcomes in patients with NSCLC: Results from the European Thoracic Oncology Platform (ETOP) Lungscape Project.
机构信息
Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom.
Department of Pathology, VU University Medical Center, Amsterdam, Netherlands.
出版信息
Lung Cancer. 2019 May;131:95-103. doi: 10.1016/j.lungcan.2019.03.012. Epub 2019 Mar 15.
INTRODUCTION
The PD-L1 biomarker is an important factor in selecting patients with non-small cell lung cancer for immunotherapy. While several reports suggest that PD-L1 positivity is linked to a poor prognosis, others suggest that PD-L1 positive status portends a good prognosis.
METHODS
PD-L1 positivity prevalence, assessed via immunohistochemistry (IHC) on tissue microarrays (TMAs), and its association with clinicopathological characteristics, molecular profiles and patient outcome- Relapse-free Survival (RFS), Time-to-Relapse (TTR) and Overall Survival (OS)- is explored in the ETOP Lungscape cohort of stage I-III non-small cell lung cancer (NSCLC). Tumors are considered positive if they have ≥1/5/25/50% neoplastic cell membrane staining.
RESULTS
PD-L1 expression was assessed in 2182 NSCLC cases (2008 evaluable, median follow-up 4.8 years, 54.6% still alive), from 15 ETOP centers. Adenocarcinomas represent 50.9% of the cohort (squamous cell: 42.4%). Former smokers are 53.7% (current: 31.6%, never: 10.5%). PD-L1 positivity prevalence is present in more than one third of the Lungscape cohort (1%/5% cut-offs). It doesn't differ between adenocarcinomas and squamous cell histologies, but is more frequently detected in higher stages, never smokers, larger tumors (1/5/25% cut-offs). With ≥1% cut-off it is significantly associated with IHC MET overexpression, expression of PTEN, EGFR and KRAS mutation (only for adenocarcinoma). Results for 5%, 25% and 50% cut-offs were similar, with MET being significantly associated with PD-L1 positivity both for AC (p < 0.001, 5%/25%/50% cut-offs) and SCC (p < 0.001, 5% & 50% cut-offs and p = 0.0017 for 25%). When adjusting for clinicopathological characteristics, a significant prognostic effect was identified in adenocarcinomas (adjusted p-values: 0.024/0.064/0.063 for RFS/TTR/OS 1% cut-off, analogous for 5%/25%, but not for 50%). Similar results obtained for the model including all histologies, but no effect was found for the squamous cell carcinomas.
CONCLUSION
PD-L1 positivity, when adjusted for clinicopathological characteristics, is associated with a better prognosis for non-metastatic adenocarcinoma patients.
简介
PD-L1 生物标志物是选择非小细胞肺癌患者进行免疫治疗的一个重要因素。虽然有几份报告表明 PD-L1 阳性与预后不良有关，但也有其他报告表明 PD-L1 阳性预示着良好的预后。
方法
通过组织微阵列（TMA）上的免疫组织化学（IHC）评估 PD-L1 阳性率，并探讨其与临床病理特征、分子谱和患者结局-无复发生存（RFS）、复发时间（TTR）和总生存（OS）的关系-在 ETOP Lungscape 队列中对 I-III 期非小细胞肺癌（NSCLC）进行研究。如果肿瘤细胞膜染色的肿瘤细胞≥1/5/25/50%，则认为肿瘤为阳性。
结果
在来自 15 个 ETOP 中心的 2182 例 NSCLC 病例（2008 例可评估，中位随访 4.8 年，54.6%仍存活）中评估了 PD-L1 表达。腺癌占队列的 50.9%（鳞癌：42.4%）。前吸烟者占 53.7%（当前：31.6%，从不：10.5%）。Lungscape 队列中超过三分之一的患者存在 PD-L1 阳性（1%/5%截止值）。它在腺癌和鳞癌之间没有差异，但在更高的分期、从不吸烟者、更大的肿瘤中更常被检测到（1%/5%/25%截止值）。对于≥1%的截止值，它与 IHC MET 过表达、PTEN、EGFR 和 KRAS 突变的表达显著相关（仅适用于腺癌）。5%、25%和 50%截止值的结果相似，MET 与 AC（p<0.001，5%/25%/50%截止值）和 SCC（p<0.001，5%和 50%截止值和 p=0.0017）中的 PD-L1 阳性均显著相关。在调整临床病理特征后，在腺癌中发现了显著的预后影响（调整后的 p 值：RFS/TTR/OS 1%截止值为 0.024/0.064/0.063，类似的 5%/25%，但 50%则无）。在包括所有组织学的模型中也获得了类似的结果，但在鳞癌中没有发现效果。
结论
在调整临床病理特征后，PD-L1 阳性与非转移性腺癌患者的预后较好相关。
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