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支气管内超声引导经支气管针吸活检与配对经支气管活检标本评估Ⅲ期和Ⅳ期肺癌程序性死亡配体-1表达的适用性:一项比较性回顾性研究

Suitability of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration versus Paired Transbronchial Biopsy Specimens for Evaluating Programmed Death Ligand-1 Expression in Stage III and IV Lung Cancer: A Comparative Retrospective Study.

作者信息

Matsuoka Hiroki, Araya Tomoyuki, Kita Toshiyuki, Terada Nanao, Yamamura Kenta, Nishikawa Shingo, Tambo Yuichi, Sone Takashi, Kimura Hideharu, Ooi Akishi, Kasashima Satomi, Kawashima Atsuhiro, Kasahara Kazuo

机构信息

Department of Respiratory Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University.

Department of Respiratory Medicine, Kanazawa University Hospital.

出版信息

J Cancer. 2021 May 27;12(15):4478-4487. doi: 10.7150/jca.55738. eCollection 2021.

Abstract

Cancer cells usually escape tumor-reactive T-cell responses using immune checkpoint proteins, such as programmed death protein-1 (PD-1) and its ligand, programmed death ligand-1 (PD-L1). These proteins can be blocked by immune checkpoint inhibitors (ICIs); the decision on ICI-based first-line treatment for advanced lung cancers depends on the PD-L1 levels in tumor specimens. Determining the PD-L1 expression conventionally requires histological specimens from resected tumors and core biopsy specimens. Non-small cell lung cancer (NSCLC) is usually diagnosed at stage III or IV; therefore, only small biopsy specimens, such as those obtained via endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are available. However, the suitability of EBUS-TBNA specimens determining the PD-L1 expression levels in advanced lung cancers remains unclear. Here, we investigated the concordance rate of PD-L1 expression between EBUS-TBNA and matched transbronchial biopsy (TBB) specimens. Using the 22C3 anti-PD-L1 antibody (immunohistochemistry), we determined the PD-L1 expression levels in paired specimens obtained from 69 patients (50 with advanced NSCLC and 19 with small cell lung cancer [SCLC]), as well as the efficacy of ICIs in these patients. The concordance rate of PD-L1 expression between the EBUS-TBNA and TBB specimens was 78.3%. The κ values referent to the PD-L1-positive expression rate between EBUS-TBNA and TBB specimens were 0.707 and 0.676 at cutoff limits of ≥1% and ≥50%, respectively. Among the 19 SCLC patients, 16 (84.2%) exhibited no PD-L1 expression in both EBUS-TBNA and TBB specimens. Notably, the progression-free survival of patients with ≥50% PD-L1 expression in the paired specimens who received ICI treatment was 8.3 months. Collectively, our results validate the use of EBUS-TBNA specimens for the determination of the PD-L1 expression levels in the context of NSCLC and SCLC.

摘要

癌细胞通常利用免疫检查点蛋白逃避肿瘤反应性T细胞反应,如程序性死亡蛋白1(PD-1)及其配体程序性死亡配体1(PD-L1)。这些蛋白可被免疫检查点抑制剂(ICI)阻断;晚期肺癌基于ICI的一线治疗决策取决于肿瘤标本中的PD-L1水平。传统上,确定PD-L1表达需要切除肿瘤的组织学标本和核心活检标本。非小细胞肺癌(NSCLC)通常在III期或IV期被诊断;因此,只有小活检标本,如通过支气管内超声引导下经支气管针吸活检(EBUS-TBNA)获得的标本可用。然而,EBUS-TBNA标本用于确定晚期肺癌中PD-L1表达水平的适用性仍不清楚。在此,我们研究了EBUS-TBNA与匹配的经支气管活检(TBB)标本中PD-L1表达的一致性率。使用22C3抗PD-L1抗体(免疫组织化学),我们确定了从69例患者(50例晚期NSCLC和19例小细胞肺癌[SCLC])获得的配对标本中PD-L1的表达水平,以及这些患者中ICI的疗效。EBUS-TBNA与TBB标本中PD-L1表达的一致性率为78.3%。在截断值≥1%和≥50%时,EBUS-TBNA与TBB标本之间PD-L1阳性表达率的κ值分别为0.707和0.676。在19例SCLC患者中,16例(84.2%)在EBUS-TBNA和TBB标本中均未表现出PD-L1表达。值得注意的是,配对标本中PD-L1表达≥50%且接受ICI治疗的患者的无进展生存期为8.3个月。总体而言,我们的结果验证了EBUS-TBNA标本在NSCLC和SCLC背景下用于确定PD-L1表达水平的用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6842/8210556/c151268412f8/jcav12p4478g001.jpg

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