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
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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. / Plage, Henning; Furlano, Kira; Hofbauer, Sebastian; Weinberger, Sarah; Ralla, Bernhard; Franz, Antonia; Fendler, Annika; de Martino, Michela; Roßner, Florian; Elezkurtaj, Sefer; Kluth, Martina; Lennartz, Maximilian; Blessin, Niclas C.; Marx, Andreas H.; Samtleben, Henrik; Fisch, Margit; Rink, Michael; Slojewski, Marcin; Kaczmarek, Krystian; Ecke, Thorsten; Hallmann, Steffen; Koch, Stefan; Adamini, Nico; Zecha, Henrik; Minner, Sarah; Simon, Ronald; Sauter, Guido; Weischenfeldt, Joachim; Klatte, Tobias; Schlomm, Thorsten; Horst, David; Schallenberg, Simon.
I: BMC Urology, Bind 24, 96, 2024.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - 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
AU - Plage, Henning
AU - Furlano, Kira
AU - Hofbauer, Sebastian
AU - Weinberger, Sarah
AU - Ralla, Bernhard
AU - Franz, Antonia
AU - Fendler, Annika
AU - de Martino, Michela
AU - Roßner, Florian
AU - Elezkurtaj, Sefer
AU - Kluth, Martina
AU - Lennartz, Maximilian
AU - Blessin, Niclas C.
AU - Marx, Andreas H.
AU - Samtleben, Henrik
AU - Fisch, Margit
AU - Rink, Michael
AU - Slojewski, Marcin
AU - Kaczmarek, Krystian
AU - Ecke, Thorsten
AU - Hallmann, Steffen
AU - Koch, Stefan
AU - Adamini, Nico
AU - Zecha, Henrik
AU - Minner, Sarah
AU - Simon, Ronald
AU - Sauter, Guido
AU - Weischenfeldt, Joachim
AU - Klatte, Tobias
AU - Schlomm, Thorsten
AU - Horst, David
AU - Schallenberg, Simon
N1 - Publisher Copyright: © The Author(s) 2024.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - Immunohistochemistry
KW - PD-L1
KW - Tissue microarray
KW - Urothelial bladder carcinomas
U2 - 10.1186/s12894-024-01482-z
DO - 10.1186/s12894-024-01482-z
M3 - Journal article
C2 - 38658905
AN - SCOPUS:85191058780
VL - 24
JO - BMC Urology
JF - BMC Urology
SN - 1471-2490
M1 - 96
ER -
ID: 392916208