Enrico Munari1, Giuseppe Zamboni2, Gianluigi Lunardi3, Luigi Marchionni4, Marcella Marconi5, Marco Sommaggio5, Matteo Brunelli6, Guido Martignoni7, George J Netto8, Mohammad O Hoque9, Francesca Moretta10, Maria Cristina Mingari11, Maria Cristina Pegoraro12, Alessandro Inno3, Simona Paiano13, Alberto Terzi14, Alberto Cavazza15, Giulio Rossi16, Francesca Romana Mariotti17, Paola Vacca17, Lorenzo Moretta17, Giuseppe Bogina5. 1. Department of Pathology, Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy; Department of Diagnostics and Public Health, University of Verona, Verona, Italy. Electronic address: enrico.munari@sacrocuore.it. 2. Department of Pathology, Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy; Department of Diagnostics and Public Health, University of Verona, Verona, Italy. 3. Department of Oncology, Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy. 4. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. 5. Department of Pathology, Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy. 6. Department of Diagnostics and Public Health, University of Verona, Verona, Italy. 7. Department of Diagnostics and Public Health, University of Verona, Verona, Italy; Department of Pathology, Pederzoli Hospital, Peschiera del Garda, Verona, Italy. 8. Department of Pathology, The University of Alabama at Birmingham, Birmingham, Alabama. 9. Department of Otolaringology, Johns Hopkins University School of Medicine, Baltimore, Maryland. 10. Department of Laboratory Medicine, Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy. 11. Department of Experimental Medicine, University of Genova, Genoa, Italy. 12. Department of Oncology, Pederzoli Hospital, Peschiera del Garda, Verona, Italy. 13. Department of Pulmonology, Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy. 14. Department of Thoracic Surgery, Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy. 15. Department of Pathology, Arcispedale S. Maria Nuova/IRCCS, Reggio Emilia, Italy. 16. Department of Pathology, AUSL della Romagna, Ravenna, Italy. 17. Immunology Research Area, IRCCS Bambino Gesù Pediatric Hospital, Rome, Italy.
Abstract
INTRODUCTION: Determination of programmed death ligand 1 (PD-L1) expression defines eligibility for treatment with pembrolizumab in patients with advanced NSCLC. This study was designed to better define which value across core biopsy specimens from the same case more closely reflects the PD-L1 expression status on whole sections and how many core biopsy specimens are needed for confident classification of tumors in terms of PD-L1 expression. METHODS: We built tissue microarrays as surrogates of biopsies collecting five cores per case from 268 cases and compared PD-L1 staining results obtained by using the validated clone SP263 with the results obtained by using whole tumor sections. RESULTS: We found an overall positivity in 39% of cases at a cutoff of 1% and in 10% of cases at a cutoff of 50%. The maximum value across cores was associated with high concordance between cores and whole sections and the lowest number of false-negative cases overall. To reach high concordance with whole sections, four and three cores are necessary at cutoffs of 1% and 50%, respectively. Importantly, with 20% as the cutoff for core biopsy specimens, fewer than three cores showed high sensitivity and specificity in identifying cases with 50% or more of tumor cells positive for PD-L1 on whole sections. Specifically, for PD-L1 expression values of 20% to 49% on cores, the probabilities of a tumor specimen expressing PD-L1 in at least 50% of cells on a whole section were 46% and 24% with one and two biopsy specimens, respectively. CONCLUSIONS: An accurate definition of the criteria to determine the PD-L1 status of a given tumor may greatly help in selecting those patients who could benefit from anti-programmed cell death 1/PD-L1 treatment.
INTRODUCTION: Determination of programmed death ligand 1 (PD-L1) expression defines eligibility for treatment with pembrolizumab in patients with advanced NSCLC. This study was designed to better define which value across core biopsy specimens from the same case more closely reflects the PD-L1 expression status on whole sections and how many core biopsy specimens are needed for confident classification of tumors in terms of PD-L1 expression. METHODS: We built tissue microarrays as surrogates of biopsies collecting five cores per case from 268 cases and compared PD-L1 staining results obtained by using the validated clone SP263 with the results obtained by using whole tumor sections. RESULTS: We found an overall positivity in 39% of cases at a cutoff of 1% and in 10% of cases at a cutoff of 50%. The maximum value across cores was associated with high concordance between cores and whole sections and the lowest number of false-negative cases overall. To reach high concordance with whole sections, four and three cores are necessary at cutoffs of 1% and 50%, respectively. Importantly, with 20% as the cutoff for core biopsy specimens, fewer than three cores showed high sensitivity and specificity in identifying cases with 50% or more of tumor cells positive for PD-L1 on whole sections. Specifically, for PD-L1 expression values of 20% to 49% on cores, the probabilities of a tumor specimen expressing PD-L1 in at least 50% of cells on a whole section were 46% and 24% with one and two biopsy specimens, respectively. CONCLUSIONS: An accurate definition of the criteria to determine the PD-L1 status of a given tumor may greatly help in selecting those patients who could benefit from anti-programmed cell death 1/PD-L1 treatment.
Authors: C Kuempers; L I S van der Linde; M Reischl; W Vogel; F Stellmacher; M Reck; D Heigener; K F Rabe; J Kirfel; S Perner; L Welker Journal: Virchows Arch Date: 2019-08-07 Impact factor: 4.064
Authors: Jiyoon Bu; Ashita Nair; Mari Iida; Woo-Jin Jeong; Michael J Poellmann; Kara Mudd; Luke J Kubiatowicz; Elizabeth W Liu; Deric L Wheeler; Seungpyo Hong Journal: Nano Lett Date: 2020-06-11 Impact factor: 11.189
Authors: Masahiro Shibata; Akira Ooki; Yoshikuni Inokawa; Pritam Sadhukhan; M Talha Ugurlu; Evgeny Izumchenko; Enrico Munari; Giuseppe Bogina; Charles M Rudin; Edward Gabrielson; Anju Singh; Mohammad O Hoque Journal: Mol Cancer Ther Date: 2020-08-26 Impact factor: 6.261
Authors: Julika Ribbat-Idel; Franz F Dressler; Rosemarie Krupar; Christian Watermann; Finn-Ole Paulsen; Patrick Kuppler; Luise Klapper; Anne Offermann; Barbara Wollenberg; Dirk Rades; Simon Laban; Markus Reischl; Karl-Ludwig Bruchhage; Christian Idel; Sven Perner Journal: Front Med (Lausanne) Date: 2021-04-27