Programmed death-ligand 1 expression profiling in thymic epithelial cell tumors: Clinicopathological features and quantitative digital image analyses. (July 2020)

• Record Type: Journal Article
• Authors: Ishihara, Shunta; Okada, Satoru; Ogi, Hiroshi; Kodama, Yoshinori; Shimomura, Masanori; Tsunezuka, Hiroaki; Itoh, Kyoko; Marx, Alexander; Inoue, Masayoshi
• Is Part Of: Lung cancer. Volume 145(2020)
• Page Start: 40
• Page End: 47
• Publication Date: 2020-07
• Subjects: TETs thymic epithelial cell tumors -- WHO World Health Organization -- TC thymic carcinomas -- NSCLC non-small cell lung cancer -- PD-L1 programmed death-ligand 1 -- WSI whole-slide imaging -- TPS tumor proportion score -- RFS recurrence-free survival -- FFPE formalin-fixed paraffin-embedded -- HE hematoxylin and eosin -- ROI region of interest; Thymoma -- Thymic epithelial tumor -- Programmed cell death ligand 1 -- Digital image analysis -- Whole-Slide imaging; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2020.04.038
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Extent of PD-L1 expression in TET was associated with histological subtype. Type B thymoma shows higher PD-L1 expression than type A thymoma/thymic carcinoma. WSI with cytokeratin stain appears available to analyze PD-L1 expression for thymoma. High PD-L1 expression in TETs was associated with poor prognosis. Abstract: 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.