M Ilie1, E Long-Mira1, C Bence2, C Butori2, S Lassalle1, L Bouhlel3, L Fazzalari4, K Zahaf2, S Lalvée2, K Washetine5, J Mouroux6, N Vénissac7, M Poudenx8, J Otto9, J C Sabourin10, C H Marquette3, V Hofman11, P Hofman12. 1. Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice IRCAN Team 3, INSERM U1081/UMR CNRS 7284, Faculty of Medicine of Nice, University of Nice Sophia Antipolis, Nice. 2. Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice. 3. IRCAN Team 3, INSERM U1081/UMR CNRS 7284, Faculty of Medicine of Nice, University of Nice Sophia Antipolis, Nice Department of Pneumology. 4. IRCAN Team 3, INSERM U1081/UMR CNRS 7284, Faculty of Medicine of Nice, University of Nice Sophia Antipolis, Nice. 5. Hospital-Related Biobank BB-0033-00025. 6. IRCAN Team 3, INSERM U1081/UMR CNRS 7284, Faculty of Medicine of Nice, University of Nice Sophia Antipolis, Nice Department of Thoracic Surgery, Pasteur Hospital, Nice. 7. Department of Thoracic Surgery, Pasteur Hospital, Nice. 8. Department of Pneumology. 9. Department of Pneumology, Centre Antoine Lacassagne, Nice. 10. Laboratory of Cancer Genetics, Department of Pathology, Rouen University Hospital, Rouen, France. 11. Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice IRCAN Team 3, INSERM U1081/UMR CNRS 7284, Faculty of Medicine of Nice, University of Nice Sophia Antipolis, Nice Hospital-Related Biobank BB-0033-00025. 12. Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice IRCAN Team 3, INSERM U1081/UMR CNRS 7284, Faculty of Medicine of Nice, University of Nice Sophia Antipolis, Nice Hospital-Related Biobank BB-0033-00025 hofman.p@chu-nice.fr.
Abstract
BACKGROUND: High expression of programmed death ligand-1 (PD-L1) on tumor cells (TC) and/or on tumor-infiltrating immune cells (IC) is associated with a high response rate in patients with advanced nonsmall-cell lung cancer (NSCLC) treated with PD-L1 inhibitors. The use of a PD-L1 immunohistochemical (IHC) test in determining the responsiveness to immunotherapy has raised the question of the reliability and reproducibility of its evaluation in lung biopsies compared with corresponding resected surgical specimens. PATIENTS AND METHODS: PD-L1 expression in TC and IC was assessed in 160 patients with operable NSCLC on both whole surgical tissue sections and matched lung biopsies, by using a highly sensitive SP142 IHC assay. The specimens were scored as TC 0-3 and IC 0-3 based on increasing PD-L1 expression. RESULTS: PD-L1 expression was frequently discordant between surgical resected and matched biopsy specimens (the overall discordance rate = 48%; 95% confidence interval 4.64-13.24) and κ value was equal to 0.218 (poor agreement). In all cases, the biopsy specimens underestimated the PD-L1 status observed on the whole tissue sample. PD-L1-positive IC tumors were more common than PD-L1-positive TC tumors on resected specimens. The discrepancies were mainly related to the lack of a PD-L1-positive IC component in matched biopsies. CONCLUSIONS: Our results indicate relatively poor association of the PD-L1 expression in TC and IC between lung biopsies and corresponding resected tumors. Although these results need to be further validated in larger cohorts, they indicate that the daily routine evaluation of the PD-L1 expression in diagnostic biopsies can be misleading in defining the sensitivity to treatment with PD-L1 targeted therapy.
BACKGROUND: High expression of programmed death ligand-1 (PD-L1) on tumor cells (TC) and/or on tumor-infiltrating immune cells (IC) is associated with a high response rate in patients with advanced nonsmall-cell lung cancer (NSCLC) treated with PD-L1 inhibitors. The use of a PD-L1 immunohistochemical (IHC) test in determining the responsiveness to immunotherapy has raised the question of the reliability and reproducibility of its evaluation in lung biopsies compared with corresponding resected surgical specimens. PATIENTS AND METHODS: PD-L1 expression in TC and IC was assessed in 160 patients with operable NSCLC on both whole surgical tissue sections and matched lung biopsies, by using a highly sensitive SP142 IHC assay. The specimens were scored as TC 0-3 and IC 0-3 based on increasing PD-L1 expression. RESULTS:PD-L1 expression was frequently discordant between surgical resected and matched biopsy specimens (the overall discordance rate = 48%; 95% confidence interval 4.64-13.24) and κ value was equal to 0.218 (poor agreement). In all cases, the biopsy specimens underestimated the PD-L1 status observed on the whole tissue sample. PD-L1-positive IC tumors were more common than PD-L1-positive TC tumors on resected specimens. The discrepancies were mainly related to the lack of a PD-L1-positive IC component in matched biopsies. CONCLUSIONS: Our results indicate relatively poor association of the PD-L1 expression in TC and IC between lung biopsies and corresponding resected tumors. Although these results need to be further validated in larger cohorts, they indicate that the daily routine evaluation of the PD-L1 expression in diagnostic biopsies can be misleading in defining the sensitivity to treatment with PD-L1 targeted therapy.
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Authors: Marius Ilie; Alexander T Falk; Catherine Butori; Emmanuel Chamorey; Christelle Bonnetaud; Elodie Long; Sandra Lassalle; Katia Zahaf; Nicolas Vénissac; Jérôme Mouroux; Charlotte Cohen; Elisabeth Brambilla; Charles Hugo Marquette; Véronique Hofman; Paul Hofman Journal: Mod Pathol Date: 2016-08-26 Impact factor: 7.842