Evaluation of the diagnostic concordance of FDA-approved PD-L1 assays in clear cell renal cell carcinoma

Abstract Therapeutic strategies for advanced renal cell carcinoma have advanced dramatically since the approval of immune checkpoint inhibitors. To date, four PD-L1 assays have been established as companion diagnostic tools for checkpoint inhibitors. However, all PD-L1 assays present several limitat...

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Main Authors: Yoko Koh, Taigo Kato, Gaku Yamamichi, Eisuke Tomiyama, Makoto Matsushita, Koji Hatano, Atsunari Kawashima, Norio Nonomura, Motohide Uemura
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-05697-4
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Summary:Abstract Therapeutic strategies for advanced renal cell carcinoma have advanced dramatically since the approval of immune checkpoint inhibitors. To date, four PD-L1 assays have been established as companion diagnostic tools for checkpoint inhibitors. However, all PD-L1 assays present several limitations in terms of concordance and compatibility. In this study, we constructed tissue microarrays from 286 clear cell renal cell carcinoma (ccRCC) tissue samples and evaluated PD-L1 expression using the 22C3, 28 − 8, SP142, and SP263 PD-L1 assays. Detection of PD-L1 expression in tumor cells was very low for all PD-L1 assays tested, although expression of PD-L1 in immune cells in the tumor area was 14.7% for 22C3, 16.1% for 28 − 8, 2.1% for SP142, and 15.0% for SP263. PD-L1 expression on immune cells assessed by 28 − 8 showed a moderate pairwise concordance with other assays (κ statistics: 0.52 with 22C3, 0.16 with SP142, and 0.46 with SP263). Patients with PD-L1 expression in immune cells evaluated using 22C3, 28 − 8, and SP263 showed significantly worse cancer-specific survival. PD-L1 expression on renal cell carcinoma tissues assessed using 22C3, 28 − 8, SP142, and SP263 did not show good concordance. In conclusion, differences between these assays should be considered when evaluating the results of immunohistochemical findings.
ISSN:2045-2322