A multicenter round robin test of PD-L1 expression assessment in urothelial bladder cancer by immunohistochemistry and RT-qPCR with emphasis on prognosis prediction after radical cystectomy

Journal article


Publication Details

Author(s): Eckstein M, Wirtz RM, Pfannstil C, Wach S, Stoehr R, Breyer J, Erlmeier F, Günes C, Nitschke K, Weichert W, Otto W, Keck B, Eidt S, Burger M, Taubert H, Wullich B, Bolenz C, Hartmann A, Erben P
Journal: Oncotarget
Publication year: 2018
Volume: 9
Journal issue: 19
Pages range: 15001-15014
ISSN: 1949-2553


Abstract

Background: Immunohistochemical PD-L1 assessment is currently used to identify responders towards checkpoint inhibitors although it is limited by inter-observer effects. Here, we conducted a multi-center round robin test to prove the possibility of assessing the PD-L1 status by gene expression to avoid inter-observer effects.
Patients and methods: Gene expression of PD-L1 was analyzed in a total of 294 samples (14 cases non-muscle invasive and muscle-invasive bladder cancer; MIBC) in seven centers by a RT-qPCR kit and compared with immunohistochemical scoring of three pathologists (DAKO, 22c3). Both assays were compared towards prognosis prediction in a cohort of 88 patients with MIBC.
Results: PD-L1 gene expression revealed very high inter center correlation (centrally extracted RNA: r = 0.68-0.98, p ≤ 0.0076; locally extracted RNA: r = 0.81-0.98, p ≤ 0.0014). IHC Inter-observer concordance was moderate to substantial for immune cells (IC), fair for combined IC/ tumor cell (TC) (IC: κ = 0.50-0.61; IC + TC: κ = 0.50), and fair for TC scoring (κ = 0.26-0.35). Gene expression assessment resulted in more positive cases (9/14 cases positive vs. 6/14 cases [IHC]) which could be validated in the independent cohort. Positive mRNA status was associated with significantly better overall and disease-specific survival (5-year OS: 50% vs. 26%, p = 0.0042, HR = 0.48; 5 year DSS: 65% vs. 40%, p = 0.012, HR = 0.49). The 1% IHC IC cut-off also revealed significant better OS (5 year OS: 58% vs. 31%, p = 0.036, HR = 0.62).
Conclusion: Gene expression showed very high inter-center agreement. Gene expression assessment also resulted in more positive cases and revealed better prognosis prediction. PD-L1 mRNA expression seems to be a reproducible and robust tool for PD-L1 assessment.


FAU Authors / FAU Editors

Eckstein, Markus Dr. med.
Pathologisches Institut
Hartmann, Arndt Prof. Dr. med.
Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie
Keck, Bastian PD Dr.
Medizinische Fakultät
Taubert, Helge Prof. Dr. rer. nat.
Urologische Klinik
Wullich, Bernd Prof. Dr.
Lehrstuhl für Urologie


External institutions with authors

Ruprecht-Karls-Universität Heidelberg
St. Elisabeth-Krankenhaus Köln-Hohenlind
Technische Universität München (TUM)
UCL Institute of Neurology
Universität Ulm


How to cite

APA:
Eckstein, M., Wirtz, R.M., Pfannstil, C., Wach, S., Stoehr, R., Breyer, J.,... Erben, P. (2018). A multicenter round robin test of PD-L1 expression assessment in urothelial bladder cancer by immunohistochemistry and RT-qPCR with emphasis on prognosis prediction after radical cystectomy. Oncotarget, 9(19), 15001-15014. https://dx.doi.org/10.18632/oncotarget.24531

MLA:
Eckstein, Markus, et al. "A multicenter round robin test of PD-L1 expression assessment in urothelial bladder cancer by immunohistochemistry and RT-qPCR with emphasis on prognosis prediction after radical cystectomy." Oncotarget 9.19 (2018): 15001-15014.

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Last updated on 2019-25-04 at 14:57

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