Multicentric Analytical and Inter-observer Comparability of Four Clinically Developed Programmed Death-ligand 1 Immunohistochemistry Assays in Advanced Clear-cell Renal Cell Carcinoma

Clinical Genitourinary Cancer, vol. 18, pp. e629–e642

Abstract

BACKGROUND: Previous studies have suggested increased clinical benefit with inhibition of programmed death-ligand 1 (PD-L1)/programmed death-1 in patients with PD-L1-positive locally advanced/metastatic renal cell carcinoma (RCC). We examined the analytical and inter-observer comparability of PD-L1-positivity across 4 clinically developed immunohistochemistry assays in clear-cell RCC (CCRCC). MATERIALS AND METHODS: Randomly selected archived, formalin-fixed, paraffin-embedded nephrectomy specimens from 201 patients with locally advanced CCRCC were screened using VENTANA SP142. From these, 30 cases were selected based on their tumor-infiltrating immune cell (IC) PD-L1 status (PD-L1-IC-positivity of < 1%, 1%-5%, or > 5%; 10 cases each). These cases were stained for PD-L1 using VENTANA SP142 and SP263, and DAKO 22C3 and 28-8, and scored for PD-L1 expression on IC and tumor cells (TC) by trained readers at 5 sites. RESULTS: Adjusted mean percentages of PD-L1-IC-positivity and PD-L1-TC-positivity varied from 4.0% to 4.9% and from 1.3% to 10.7%, respectively, between assays. Inter-assay differences in PD-L1-IC-positivity were small and non-significant (P = .1938 to .9963); for PD-L1-TC-positivity, significant differences were observed between VENTANA SP142 and the other assays (P ≤ .0001) and between VENTANA SP263 and DAKO 28-8 (P = .0248). Intra-class correlation values showed moderate-to-high inter-reader agreement for each assay for PD-L1-IC-positivity and for 3 assays for PD-L1-TC-positivity. CONCLUSIONS: In this first multicenter analytical comparison study of PD-L1 assays in CCRCC, PD-L1-positivity could be assessed reproducibly using all 4 assays for IC and for 3 of the 4 assays for TC.

Authors 16

1. Ulrich J. Sommer

   University Hospital Carl Gustav Carus

   Affiliation as printed

   Institute of Pathology, Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Germany

2. Markus Eckstein

   Friedrich-Alexander-Universität Erlangen-Nürnberg · Universitätsklinikum Erlangen

   Affiliation as printed

   Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

3. Johannes U Ammann corresponding

   Roche Pharma AG (Germany)

   Affiliation as printed

   Roche Pharma AG, Grenzach-Wyhlen, Germany. Electronic address: johannes.ammann@roche.com

   Roche Pharma AG, Grenzach-Wyhlen, Germany

4. Till A. Braunschweig Aachen Institute of Pathology

   Universitätsklinikum Aachen

   Affiliation as printed

   Institute of Pathology, Uniklinik RWTH Aachen, Aachen, Germany

5. Stephan Macher-Göppinger

   Johannes Gutenberg University Mainz · University Medical Center of the Johannes Gutenberg University Mainz

   Affiliation as printed

   Institute of Pathology, Universitätsmedizin Mainz, Mainz, Germany

6. Kristina Schwamborn

   Technical University of Munich

   Affiliation as printed

   Technische Universität München, School of Medicine, Institute of Pathology, Munich, Germany

7. Stefanie Hieke‐Schulz

   Roche Pharma AG (Germany)

   Affiliation as printed

   Roche Pharma AG, Grenzach-Wyhlen, Germany

8. Greg Harlow

   Ventana Research Corporation (United States)

   Affiliation as printed

   Ventana Medical Systems, Inc, Tucson, AZ

9. Mike Flores

   Ventana Research Corporation (United States)

   Affiliation as printed

   Ventana Medical Systems, Inc, Tucson, AZ

10. Bernd Wullich

    Friedrich-Alexander-Universität Erlangen-Nürnberg · Universitätsklinikum Erlangen

    Affiliation as printed

    Department of Urology and Pediatric Urology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

11. Manfred Peter Wirth

    University Hospital Carl Gustav Carus

    Affiliation as printed

    Department of Urology, Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Germany

12. Wilfried Roth

    Johannes Gutenberg University Mainz · University Medical Center of the Johannes Gutenberg University Mainz

    Affiliation as printed

    Institute of Pathology, Universitätsmedizin Mainz, Mainz, Germany

13. Ruth Knüchel Aachen Institute of Pathology

    Universitätsklinikum Aachen

    Affiliation as printed

    Institute of Pathology, Uniklinik RWTH Aachen, Aachen, Germany

14. Wilko Weichert

    Technical University of Munich

    Affiliation as printed

    Technische Universität München, School of Medicine, Institute of Pathology, Munich, Germany

15. Gustavo Bruno Baretton

    University Hospital Carl Gustav Carus

    Affiliation as printed

    Institute of Pathology, Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Germany

16. Arndt Hartmann

    Friedrich-Alexander-Universität Erlangen-Nürnberg · Universitätsklinikum Erlangen

    Affiliation as printed

    Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany