PMID- 32402921 OWN - NLM STAT- MEDLINE DCOM- 20210621 LR - 20220531 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 145 DP - 2020 Jul TI - Programmed death-ligand 1 expression profiling in thymic epithelial cell tumors: Clinicopathological features and quantitative digital image analyses. PG - 40-47 LID - S0169-5002(20)30408-6 [pii] LID - 10.1016/j.lungcan.2020.04.038 [doi] AB - OBJECTIVES: Whether the extent of expression of programmed death-ligand 1 (PD-L1) is clinically significant remains uncertain, although immuno-oncological features have been studied in thymic epithelial cell tumors (TETs). We investigated the histological features of PD-L1 expression in TETs, and assessed PD-L1 expression using digital image analysis. MATERIALS AND METHODS: Participants comprised 66 patients with TET who underwent surgical resection between 2001 and 2016. We calculated tumor cell-positive ratio as total proportion score (TPS) with immunohistochemistry using SP263 anti-PD-L1 monoclonal antibody. PD-L1 expression was also quantified using digital image analysis of whole-slide images. We evaluated the relationship between conventional visual TPS using optical microscopy (TPS-V) and TPS from digital image analysis (TPS-IA). We further classified all TETs into high or low PD-L1 expression groups and assessed the clinical significance of PD-L1 expression level using TPS-V and TPS-IA. RESULTS: WHO histological types were Type A (n = 8), AB (n = 18), B1 (n = 5), B2 (n = 16), B3 (n = 6), metaplastic thymoma (n = 2), and thymic carcinoma (TC) (n = 11). Median TPS-Vs were 2%, 2%, 10 %, 65 %, 90 %, 1%, and 20 %, respectively. TPS-IAs correlated with TPS-Vs in TETs overall and in thymomas, but not in TCs. PD-L1 expression levels in TETs differed significantly among histological types. Whether TPS-V or TPS-IA were used, the PD-L1(high) group included more cases of the more aggressive histological types. Recurrence-free survival (RFS) was shorter in the PD-L1(high) group than in the PD-L1(low) group in thymoma using TPS-IA, whereas RFS of the PD-L1(high) group was shorter in all TETs using TPS-V. CONCLUSION: PD-L1 expression levels depended on the histological type of TET. Extensive PD-L1 expression in TETs was associated with poor prognosis. Digital image analysis is feasible for evaluating PD-L1 expression in TETs and might offer clinically relevant features of thymomas. CI - Copyright (c) 2020 Elsevier B.V. All rights reserved. FAU - Ishihara, Shunta AU - Ishihara S AD - Division of Thoracic Surgery, Department of Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan. FAU - Okada, Satoru AU - Okada S AD - Division of Thoracic Surgery, Department of Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan. FAU - Ogi, Hiroshi AU - Ogi H AD - Department of Pathology and Applied Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan. FAU - Kodama, Yoshinori AU - Kodama Y AD - Department of Pathology and Applied Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan. FAU - Shimomura, Masanori AU - Shimomura M AD - Division of Thoracic Surgery, Department of Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan. FAU - Tsunezuka, Hiroaki AU - Tsunezuka H AD - Division of Thoracic Surgery, Department of Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan. FAU - Itoh, Kyoko AU - Itoh K AD - Department of Pathology and Applied Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan. FAU - Marx, Alexander AU - Marx A AD - Institute of Pathology, University Medical Centre Mannheim, Heidelberg University, Mannheim, Germany. FAU - Inoue, Masayoshi AU - Inoue M AD - Division of Thoracic Surgery, Department of Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan. Electronic address: mainoue@koto.kpu-m.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200506 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - 0 (B7-H1 Antigen) RN - 0 (CD274 protein, human) SB - IM MH - B7-H1 Antigen MH - Epithelial Cells MH - Humans MH - *Lung Neoplasms MH - *Thymoma MH - *Thymus Neoplasms OTO - NOTNLM OT - Digital image analysis OT - Programmed cell death ligand 1 OT - Thymic epithelial tumor OT - Thymoma OT - Whole-Slide imaging COIS- Declaration of Competing Interest The authors have no conflicts of interest. EDAT- 2020/05/14 06:00 MHDA- 2021/06/22 06:00 CRDT- 2020/05/14 06:00 PHST- 2019/12/02 00:00 [received] PHST- 2020/04/26 00:00 [revised] PHST- 2020/04/28 00:00 [accepted] PHST- 2020/05/14 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/05/14 06:00 [entrez] AID - S0169-5002(20)30408-6 [pii] AID - 10.1016/j.lungcan.2020.04.038 [doi] PST - ppublish SO - Lung Cancer. 2020 Jul;145:40-47. doi: 10.1016/j.lungcan.2020.04.038. Epub 2020 May 6.