PD-L1 expression in tumor and inflammatory cells is associated with favorable tumor features and favorable prognosis in muscle-invasive urothelial carcinoma of the bladder not treated by immune checkpoint inhibitors
Henning Plage,
Kira Furlano,
Sebastian Hofbauer,
Sarah Weinberger,
Bernhard Ralla,
Antonia Franz,
Annika Fendler,
Michela de Martino,
Florian Roßner,
Sefer Elezkurtaj,
Martina Kluth,
Maximilian Lennartz,
Niclas C. Blessin,
Andreas H. Marx,
Henrik Samtleben,
Margit Fisch,
Michael Rink,
Marcin Slojewski,
Krystian Kaczmarek,
Thorsten Ecke,
Steffen Hallmann,
Stefan Koch,
Nico Adamini,
Henrik Zecha,
Sarah Minner,
Ronald Simon,
Guido Sauter,
Joachim Weischenfeldt,
Tobias Klatte,
Thorsten Schlomm,
David Horst,
Simon Schallenberg
Affiliations
Henning Plage
Department of Urology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
Kira Furlano
Department of Urology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
Sebastian Hofbauer
Department of Urology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
Sarah Weinberger
Department of Urology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
Bernhard Ralla
Department of Urology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
Antonia Franz
Department of Urology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
Annika Fendler
Department of Urology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
Michela de Martino
Department of Urology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
Florian Roßner
Institute of Pathology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
Sefer Elezkurtaj
Institute of Pathology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
Martina Kluth
Institute of Pathology, University Medical Center Hamburg-Eppendorf
Maximilian Lennartz
Institute of Pathology, University Medical Center Hamburg-Eppendorf
Niclas C. Blessin
Institute of Pathology, University Medical Center Hamburg-Eppendorf
Andreas H. Marx
Department of Pathology, Academic Hospital Fuerth
Henrik Samtleben
Department of Pathology, Academic Hospital Fuerth
Margit Fisch
Department of Urology, University Medical Center Hamburg-Eppendorf
Michael Rink
Department of Urology, Marienhospital Hamburg
Marcin Slojewski
Department of Urology and Urological Oncology, Pomeranian Medical University
Krystian Kaczmarek
Department of Urology and Urological Oncology, Pomeranian Medical University
Thorsten Ecke
Department of Urology, Helios Hospital Bad Saarow
Steffen Hallmann
Department of Urology, Helios Hospital Bad Saarow
Stefan Koch
Department of Pathology, Helios Hospital Bad Saarow
Nico Adamini
Department of Urology, Albertinen Hospital
Henrik Zecha
Department of Urology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
Sarah Minner
Institute of Pathology, University Medical Center Hamburg-Eppendorf
Ronald Simon
Institute of Pathology, University Medical Center Hamburg-Eppendorf
Guido Sauter
Institute of Pathology, University Medical Center Hamburg-Eppendorf
Joachim Weischenfeldt
Department of Urology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
Tobias Klatte
Department of Urology, Helios Hospital Bad Saarow
Thorsten Schlomm
Department of Urology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
David Horst
Institute of Pathology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
Simon Schallenberg
Institute of Pathology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
Abstract Background A high level of PD-L1 expression is the most relevant predictive parameter for response to immune checkpoint inhibitor (CPI) therapy in urinary bladder cancer. Existing data on the relationship between PD-L1 expression and the natural course of disease are controversial and sparse. Methods To expand our understanding of the relationship between PD-L1 expression and parameters of cancer aggressiveness, PD-L1 was analyzed on tissue microarrays containing 2710 urothelial bladder carcinomas including 512 patients with follow-up data who underwent radical cystectomy and follow-up therapies in the pre-immune checkpoint inhibitor therapy era. Results Tumor cell positivity in ≥10% of cells were seen in 513 (20%) and an immune cell positivity occurred in 872 (34%) of 2566 interpretable cancers. PD-L1 positivity in tumor cells increased from pTaG2 low grade (0.9% positive) to pTaG3 high grade (4.1%; p = 0.0255) and was even higher in muscle-invasive (pT2–4) carcinomas (29.3%; p < 0.0001). However, within pT2–4 carcinomas, PD-L1 positivity was linked to low pT stage (p = 0.0028), pN0 (p < 0.0001), L0 status (p = 0.0005), and a better prognosis within 512 patients with cystectomy who never received CPIs (p = 0.0073 for tumor cells and p = 0.0086 for inflammatory cells). PD-L1 staining in inflammatory cells was significantly linked to PD-L1 staining in tumor cells (p < 0.0001) and both were linked to a positive p53 immunostaining (p < 0.0001). Conclusion It cannot be fully excluded that the strong statistical link between PD-L1 status and favorable histological tumor features as well as better prognosis could influence the outcome of studies evaluating CPIs in muscle-invasive urothelial carcinoma.
