Ulrich Sommer1, Markus Eckstein2, Johannes Ammann3, Till Braunschweig4, Stephan Macher-Göppinger5, Kristina Schwamborn6, Stefanie Hieke-Schulz7, Greg Harlow8, Mike Flores8, Bernd Wullich9, Manfred Wirth10, Wilfried Roth5, Ruth Knüchel4, Wilko Weichert6, Gustavo Baretton1, Arndt Hartmann2. 1. Institute of Pathology, Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Germany. 2. Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany. 3. Roche Pharma AG, Grenzach-Wyhlen, Germany. Electronic address: johannes.ammann@roche.com. 4. Institute of Pathology, Uniklinik RWTH Aachen, Aachen, Germany. 5. Institute of Pathology, Universitätsmedizin Mainz, Mainz, Germany. 6. Technische Universität München, School of Medicine, Institute of Pathology, Munich, Germany. 7. Roche Pharma AG, Grenzach-Wyhlen, Germany. 8. Ventana Medical Systems, Inc, Tucson, AZ. 9. Department of Urology and Pediatric Urology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany. 10. Department of Urology, Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Germany.
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.
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: Mieke R Van Bockstal; Maxine Cooks; Iris Nederlof; Mariël Brinkhuis; Annemiek Dutman; Monique Koopmans; Loes Kooreman; Bert van der Vegt; Leon Verhoog; Celine Vreuls; Pieter Westenend; Marleen Kok; Paul J van Diest; Inne Nauwelaers; Nele Laudus; Carsten Denkert; David Rimm; Kalliopi P Siziopikou; Scott Ely; Dimitrios Zardavas; Mustimbo Roberts; Giuseppe Floris; Johan Hartman; Balazs Acs; Dieter Peeters; John M S Bartlett; Els Dequeker; Roberto Salgado; Fabiola Giudici; Stefan Michiels; Hugo Horlings; Carolien H M van Deurzen Journal: Cancers (Basel) Date: 2021-09-29 Impact factor: 6.639