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程序性细胞死亡配体 1(PD-L1)的表达与肺腺癌中的 RAS/TP53 突变相关。

Programmed cell death-ligand 1 (PD-L1) expression is associated with RAS/TP53 mutations in lung adenocarcinoma.

机构信息

Service de pathologie et de neuropathologie est, Hospices Civils de Lyon, Lyon, France; Lyon 1 University, Lyon, France.

Lyon 1 University, Lyon, France; Service de pneumologie, Groupement hospitalier Est, Hospices Civils de Lyon, Lyon, France.

出版信息

Lung Cancer. 2018 Apr;118:62-68. doi: 10.1016/j.lungcan.2018.02.005. Epub 2018 Feb 6.

Abstract

INTRODUCTION

The systematic assessment of anti-programmed cell death ligand 1 (PD-L1) expression by immunohistochemistry (IHC) in lung adenocarcinomas is becoming standard practice. However, the assessment of PD-L1 expression on small tissue specimens needs to be evaluated and the association with other features more thoroughly analyzed.

METHODS

This retrospective single center study evaluated the immunohistochemical expression of the SP263 anti-PD-L1 antibody on tissue microarrays (TMA) of 152 surgically resected lung adenocarcinomas, using a 25% positivity threshold. The positive cases and 50 randomly chosen negative cases in tissue microarray (TMA) were reassessed on whole tissue sections. The results were correlated to clinical, histopathological and to molecular data obtained through the screening of 214 mutations in 26 genes (LungCarta panel, Agena Biosciences).

RESULTS

Among 152 primary lung adenocarcinomas, 19 cases (13%) showed PD-L1 expression. The agreement between TMA and whole tissue sections was 89%, specificity was 97%. PD-L1 expression was correlated to RAS mutations (p = .04), RAS/TP53 co-mutations (p = .01) and to the solid or acinar subtype (p = .048).

CONCLUSIONS

With the SP263 PD-L1 antibody, small samples appear as a reliable means to evaluate the PD-L1 status in lung adenocarcinoma. The association between PD-L1 expression and RAS/TP53 mutations may have clinical relevance to predict the efficacy of PD-1/PD-L1 immune checkpoints inhibitors.

摘要

简介

系统评估肺腺癌中程序性死亡配体 1(PD-L1)的免疫组织化学(IHC)表达正在成为标准做法。然而,需要评估小组织标本上 PD-L1 表达的评估,并更彻底地分析与其他特征的关联。

方法

这项回顾性单中心研究评估了 SP263 抗 PD-L1 抗体在 152 例手术切除的肺腺癌组织微阵列(TMA)上的免疫组织化学表达,使用 25%的阳性阈值。在组织切片上重新评估 TMA 中的阳性病例和 50 个随机选择的阴性病例。结果与通过 26 个基因(LungCarta 面板,Agena Biosciences)中的 214 个突变进行筛选获得的临床、组织病理学和分子数据相关联。

结果

在 152 例原发性肺腺癌中,有 19 例(13%)显示 PD-L1 表达。TMA 与全组织切片之间的一致性为 89%,特异性为 97%。PD-L1 表达与 RAS 突变相关(p=0.04)、RAS/TP53 共突变相关(p=0.01)和实性或腺泡亚型相关(p=0.048)。

结论

使用 SP263 PD-L1 抗体,小样本似乎是评估肺腺癌 PD-L1 状态的可靠手段。PD-L1 表达与 RAS/TP53 突变之间的关联可能与预测 PD-1/PD-L1 免疫检查点抑制剂的疗效具有临床相关性。

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