Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan; Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Lung Cancer. 2019 Aug;134:202-209. doi: 10.1016/j.lungcan.2019.06.002. Epub 2019 Jun 5.
Most patients with non-small cell lung cancer (NSCLC) are diagnosed at advanced stages where small biopsy specimens obtained through endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are sometimes the only available samples for diagnosis. We aimed to determine whether EBUS-TBNA specimens are suitable for the evaluation of PD-L1 protein expression and copy number alterations (CNAs).
PD-L1 protein expression and CNAs in 71 EBUS-TBNA specimens of NSCLC were assessed. Sixty-eight corresponding transbronchial biopsy (TBB) specimens from primary sites, thirteen resected primary tumors, and six resected metastases were comparatively analyzed. PD-L1 expression in tumor cells was assessed by immunohistochemistry (E1L3N). Positivity of ≥1% was used as the cutoff. PD-L1 CNAs were assessed with fluorescent in situ hybridization and were classified into three categories: amplification, polysomy, and disomy. Concordance between EBUS-TBNA and other specimens was calculated.
The cohort comprised 48 men (67.6%), 15 never-smokers (21.1%), and 39 adenocarcinomas (54.9%). The concordance of PD-L1 positivity between EBUS-TBNA and other specimens was moderate; κ = 0.63 for EBUS-TBNA vs. TBB, κ = 0.68 for EBUS-TBNA vs. resected primary tumors, and κ = 1.0 for EBUS-TBNA vs. resected metastases. The concordance of PD-L1 CNA status was comparable with that of PD-L1 expression: κ = 0.60 for EBUS-TBNA vs. TBB and κ = 0.74 for EBUS-TBNA vs. resected primary tumors. When PD-L1 copy number was assessed as a continuous variable, the correlation of PD-L1 CNAs was superior to that of PD-L1 expression. Intratumorally, PD-L1 copy number was less heterogeneous than protein expression in whole sections of resected tumors.
EBUS-TBNA specimens can be used to assess PD-L1 CNAs and protein expression. Although spatial heterogeneity should be considered for accurate interpretation, the evaluation of PD-L1 CNAs provides more reproducible results than that of protein expression levels especially with regard to intratumoral heterogeneity.
大多数非小细胞肺癌（NSCLC）患者在晚期被诊断出来，此时通过支气管内超声引导经支气管针吸活检（EBUS-TBNA）获得的小活检标本有时是唯一可用于诊断的样本。我们旨在确定 EBUS-TBNA 标本是否适合评估 PD-L1 蛋白表达和拷贝数改变（CNAs）。
评估了 71 例 NSCLC 的 EBUS-TBNA 标本中的 PD-L1 蛋白表达和 CNAs。比较分析了 68 例来自原发部位的经支气管活检（TBB）标本、13 例切除的原发肿瘤和 6 例切除的转移瘤。通过免疫组织化学（E1L3N）评估肿瘤细胞中的 PD-L1 表达。≥1%的阳性率被用作截断值。使用荧光原位杂交评估 PD-L1 CNA，并将其分为扩增、多倍体和二倍体。计算 EBUS-TBNA 与其他标本之间的一致性。
该队列包括 48 名男性（67.6%）、15 名从不吸烟者（21.1%）和 39 名腺癌（54.9%）。PD-L1 阳性率在 EBUS-TBNA 与其他标本之间的一致性为中等；EBUS-TBNA 与 TBB 的κ值为 0.63，EBUS-TBNA 与切除的原发肿瘤的κ值为 0.68，EBUS-TBNA 与切除的转移瘤的κ值为 1.0。PD-L1 CNA 状态的一致性与 PD-L1 表达的一致性相当：EBUS-TBNA 与 TBB 的κ值为 0.60，EBUS-TBNA 与切除的原发肿瘤的κ值为 0.74。当 PD-L1 拷贝数被评估为连续变量时，PD-L1 CNA 的相关性优于 PD-L1 表达。在肿瘤内，PD-L1 拷贝数在整个切除肿瘤的组织切片中比蛋白表达更均匀。
EBUS-TBNA 标本可用于评估 PD-L1 CNA 和蛋白表达。尽管为了准确解释需要考虑空间异质性，但 PD-L1 CNA 的评估提供了比蛋白表达水平更具重现性的结果，特别是在肿瘤内异质性方面。
