Scoring of PD-L1 expression intensity on pulmonary adenocarcinomas and the correlations with clinicopathological factors.
Scoring of PD-L1 expression intensity on pulmonary adenocarcinomas and the correlations with clinicopathological factors.
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DOI：
10.1136/esmoopen-2016-000083
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发表时间：
2016
期刊：
影响因子：
7.3
通讯作者：
Daigo Y
中科院分区：
文献类型：
--
作者：
Igarashi T;Teramoto K;Ishida M;Hanaoka J;Daigo Y
程序性细胞死亡配体-1(PD-L1)免疫检查点分子在非小细胞肺癌(NSCLC)进展中的作用尚未阐明，部分原因是缺乏一个标准化的方法来评估PD-L1的表达。在这项研究中，我们开发了一种新的方法来评估非小细胞肺癌细胞上PD-L1的表达，并研究了其与临床病理特征的相关性。对106例手术切除的肺腺癌进行PD-L1免疫组织化学检测后，根据PD-L1在肺泡巨噬细胞上持续表达的结果，将肿瘤细胞的PD-L1染色强度与肺泡巨噬细胞中PD-L1染色强度分为4个水平，并对PD-L1表达评分(范围0~300)进行半定量评价。分析PD-L1表达评分与临床病理特征的关系。标本中几乎所有的肺泡巨噬细胞均呈PD-L1中至强染色，为PD-L1免疫组织化学内阳性对照。分化程度为G2/3的肿瘤PD-L1表达积分(中位数)显著高于G1期(p=0.022)，有淋巴管侵袭者高于无浸润者(p=0.032)。PD-L1表达评分高的患者术后无复发生存期明显短于PD-L1表达评分低的患者(p=0.035)。吸烟习惯、组织学亚型和表皮生长因子受体突变状态与PD-L1表达评分无关。鉴于PD-L1在肺腺癌细胞中表达的异质性，肿瘤细胞上PD-L1相对肺泡巨噬细胞的表达评分似乎是肺腺癌患者PD-L1状态的一个有效指标，并显示出与肿瘤进展相关的多个因素的显著相关性。
The contribution of programmed cell death ligand-1 (PD-L1) immune checkpoint molecule toward progression of non-small cell lung cancer (NSCLC) has not yet been elucidated, in part, because of lack of a standardised method to evaluate PD-L1 expression. In this study, we developed a novel method for the evaluation of PD-L1 expression on NSCLC cells and examined its correlation with clinicopathological characteristics. After immunohistochemical examination of PD-L1 expression for surgically resected pulmonary adenocarcinomas (n=106), based on the findings that PD-L1 are consistently expressed on alveolar macrophages, PD-L1 staining intensity of tumour cells was classified into four levels relative to PD-L1 staining intensity in alveolar macrophages; PD-L1 expression scores (range, 0–300) were semiquantitatively assessed. An analysis of statistical association between PD-L1 expression score and clinicopathological characteristics was performed. Almost all of the alveolar macrophages in the specimens were moderately to strongly stained with PD-L1, serving as an internal positive control in the immunohistochemistry of PD-L1. PD-L1 expression score (median, 52.3) was significantly higher in tumours with G2/3 differentiation than in those with G1 (p=0.022) and higher in those with lymphatic invasion than in those without invasion (p=0.032). Postoperative relapse-free survival was significantly shorter in patients with a high PD-L1 expression score than in those with low PD-L1 expression score (p=0.035). Smoking habits, histological subtype, and epidermal growth factor receptor mutation status were not associated with PD-L1 expression score. Given the heterogeneous distribution of PD-L1 expression in pulmonary adenocarcinoma cells, the scoring of PD-L1 expression on tumour cells relative to that in alveolar macrophages appears to be a valid indicator of PD-L1 status of patients with pulmonary adenocarcinomas, demonstrating a significant correlation with several factors associated with tumour progression.