• Katsuhiro Yoshimura, Yusuke Inoue, Masato Karayama, Kazuo Tsuchiya, Kazutaka Mori, Yuzo Suzuki, Yuji Iwashita, Tomoaki Kahyo, Akikazu Kawase, Masayuki Tanahashi, Hiroshi Ogawa, Koushi Yokomura, Naoki Inui, Kazuhito Funai, Kazuya Shinmura, Hiroshi Niwa, Takafumi Suda, and Haruhiko Sugimura.
• Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan; Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
• Lung Cancer. 2019 Aug 1; 134: 202-209.

ObjectivesMost 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).Materials And MethodsPD-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.ResultsThe 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.ConclusionEBUS-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.Copyright © 2019 Elsevier B.V. All rights reserved.

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