David M Hwang1, Tahani Albaqer2, Rex C Santiago3, Jessica Weiss4, Jeffrey Tanguay5, Michael Cabanero6, Yuki Leung4, Prodipto Pal6, Zanobia Khan6, Sally C M Lau7, Adrian Sacher7, Emina Torlakovic8, Carol Cheung6, Ming-Sound Tsao9. 1. Department of Pathology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Laboratory Medicine & Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. 2. Department of Pathology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Pathology, Kuwait Cancer Control Center, Kuwait City, Kuwait. 3. Department of Pathology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Institute of Pathology, St. Luke's Medical Center, Quezon City, Philippines. 4. Department of Pathology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. 5. Department of Pathology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada. 6. Department of Pathology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. 7. Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. 8. Department of Pathology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Department of Pathology and Laboratory Medicine, Saskatchewan Health Authority and College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. 9. Department of Pathology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. Electronic address: ming.tsao@uhn.ca.
Abstract
INTRODUCTION: Programmed death-ligand 1 (PD-L1) is used as a biomarker for anti-programmed cell death protein-1 (PD-1) or anti-PD-L1 immunotherapies in NSCLC. We report here the results of population-based PD-L1 testing using the 22C3 IHC pharmDx Assay (Agilent Technologies) in a large Canadian regional reference pathology laboratory. METHODS: Testing was conducted reflexively on biopsies and resections for NSCLC during an 8-month period. Tumor proportion score (TPS) cutoffs for low and high expression were 1% and 50%, respectively. RESULTS: Altogether, 2031 PD-L1 tests were performed on specimens from 1795 patients, with 107 inconclusive results (5.3%). Excluding cases with inconclusive/missing data, proportions for the remaining 1713 patients were 41.6% for TPS less than 1%, 28.6% for TPS 1% to 49%, and 29.8% for TPS greater than or equal to 50%. Higher PD-L1 expression rates were noted in EGFR wild-type versus mutant tumors (p < 0.001), squamous versus adenocarcinoma (p < 0.001), and metastatic versus primary tumors (p < 0.001). PD-L1 among 103 patients with paired biopsy and resection specimens revealed moderate concordance (κ = 0.67). A total of 52% (25 of 48) of biopsies with TPS less than 1% had TPS greater than 1% in resection, whereas 84.6% (22 of 26) of biopsies with TPS greater than or equal to 50% were concordant in resected tumors. Discordance rates between biopsy and resection were 71.4% for biopsies with less than 8 mm2 total area, compared with 33.3% for biopsies with greater than or equal to 8 mm2 area (p < 0.026). Concordance among 27 patients with paired primary lung and metastatic tumor biopsies revealed only weak concordance (κ = 0.48). CONCLUSIONS: Intratumoral heterogeneity of PD-L1 expression may result in misclassification of PD-L1 status in a substantial proportion of PD-L1-negative small biopsy samples. Biopsy of metastatic site may increase proportion of patients with high PD-L1 expression.
INTRODUCTION: Programmed death-ligand 1 (PD-L1) is used as a biomarker for anti-programmed cell death protein-1 (PD-1) or anti-PD-L1 immunotherapies in NSCLC. We report here the results of population-based PD-L1 testing using the 22C3 IHC pharmDx Assay (Agilent Technologies) in a large Canadian regional reference pathology laboratory. METHODS: Testing was conducted reflexively on biopsies and resections for NSCLC during an 8-month period. Tumor proportion score (TPS) cutoffs for low and high expression were 1% and 50%, respectively. RESULTS: Altogether, 2031 PD-L1 tests were performed on specimens from 1795 patients, with 107 inconclusive results (5.3%). Excluding cases with inconclusive/missing data, proportions for the remaining 1713 patients were 41.6% for TPS less than 1%, 28.6% for TPS 1% to 49%, and 29.8% for TPS greater than or equal to 50%. Higher PD-L1 expression rates were noted in EGFR wild-type versus mutant tumors (p < 0.001), squamous versus adenocarcinoma (p < 0.001), and metastatic versus primary tumors (p < 0.001). PD-L1 among 103 patients with paired biopsy and resection specimens revealed moderate concordance (κ = 0.67). A total of 52% (25 of 48) of biopsies with TPS less than 1% had TPS greater than 1% in resection, whereas 84.6% (22 of 26) of biopsies with TPS greater than or equal to 50% were concordant in resected tumors. Discordance rates between biopsy and resection were 71.4% for biopsies with less than 8 mm2 total area, compared with 33.3% for biopsies with greater than or equal to 8 mm2 area (p < 0.026). Concordance among 27 patients with paired primary lung and metastatic tumor biopsies revealed only weak concordance (κ = 0.48). CONCLUSIONS: Intratumoral heterogeneity of PD-L1 expression may result in misclassification of PD-L1 status in a substantial proportion of PD-L1-negative small biopsy samples. Biopsy of metastatic site may increase proportion of patients with high PD-L1 expression.
Authors: Mohammed S I Mansour; Karina Malmros; Ulrich Mager; Kajsa Ericson Lindquist; Kim Hejny; Benjamin Holmgren; Tomas Seidal; Annika Dejmek; Katalin Dobra; Maria Planck; Hans Brunnström Journal: Int J Mol Sci Date: 2022-04-19 Impact factor: 6.208
Authors: Shelley Kuang; Andrea S Fung; Kirstin A Perdrizet; Kaitlin Chen; Janice J N Li; Lisa W Le; Michael Cabanero; Ola Abu Al Karsaneh; Ming S Tsao; Josh Morganstein; Laura Ranich; Adam C Smith; Cuihong Wei; Carol Cheung; Frances A Shepherd; Geoffrey Liu; Penelope Bradbury; Prodipto Pal; Joerg Schwock; Adrian G Sacher; Jennifer H Law; Tracy L Stockley; Natasha B Leighl Journal: Curr Oncol Date: 2022-06-22 Impact factor: 3.109
Authors: Miguel Garcia-Pardo; Kasia Czarnecka; Jennifer H Law; Alexandra Salvarrey; Roxanne Fernandes; Jason Fan; Lucy Corke; Thomas K Waddell; Kazuhiro Yasufuku; Laura L Donahoe; Andrew Pierre; Lisa W Le; Noor Ghumman; Geoffrey Liu; Frances A Shepherd; Penelope Bradbury; Adrian Sacher; Tracy Stockley; Prodipto Pal; Patrik Rogalla; Ming Sound Tsao; Natasha B Leighl Journal: Ther Adv Med Oncol Date: 2022-09-20 Impact factor: 5.485