Wendy A Cooper1, Thang Tran2, Ricardo E Vilain3, Jason Madore4, Christina I Selinger2, Maija Kohonen-Corish5, PoYee Yip6, Bing Yu7, Sandra A O'Toole8, Brian C McCaughan9, Jennifer H Yearley10, Lisa G Horvath11, Steven Kao11, Michael Boyer11, Richard A Scolyer3. 1. Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia; Sydney Medical School, University of Sydney, Sydney, NSW, Australia; School of Medicine, The University of Western Sydney, Sydney, NSW, Australia. Electronic address: wendy.cooper@sswahs.nsw.gov.au. 2. Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia. 3. Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia; Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Melanoma Institute Australia, Sydney, NSW, Australia. 4. Melanoma Institute Australia, Sydney, NSW, Australia. 5. School of Medicine, The University of Western Sydney, Sydney, NSW, Australia; Kinghorn Cancer Centre and Garvan Institute of Medical Research, Sydney, NSW, Australia; UNSW Medicine, UNSW Australia, Sydney, NSW, Australia. 6. Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Department of Medical Oncology, Chris O'Brien Lifehouse and Royal Prince Alfred Hospital, Camperdown, Sydney, NSW, Australia; Kinghorn Cancer Centre and Garvan Institute of Medical Research, Sydney, NSW, Australia; Macarthur Cancer Therapy Centre, Campbelltown Hospital, Sydney, NSW, Australia. 7. Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Medical Genomics, Royal Prince Alfred Hospital, Camperdown, NSW, Australia. 8. Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia; Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Kinghorn Cancer Centre and Garvan Institute of Medical Research, Sydney, NSW, Australia. 9. Sydney Cardiothoracic Surgeons, Royal Prince Alfred Medical Centre, Sydney, NSW, Australia. 10. Merck & Co. Inc., Whitehouse Station, NJ, USA. 11. Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Department of Medical Oncology, Chris O'Brien Lifehouse and Royal Prince Alfred Hospital, Camperdown, Sydney, NSW, Australia.
Abstract
OBJECTIVES: Immune checkpoint blockade using inhibitors of programmed death-1 have shown promise in early phase clinical trials in NSCLC and programmed death-ligand 1 (PD-L1) tumoral expression could potentially be a useful predictive marker. Data reporting the prevalence of PD-L1 expression in NSCLC and clinicopathologic associations is very limited. We sought to determine the frequency of PD-L1 expression in NSCLC and investigate associations with clinicopathologic features and patient outcome. MATERIALS AND METHODS: PD-L1 expression was analyzed using immunohistochemistry (Merck; clone 22C3) in 678 stages I-III NSCLC and 52 paired nodal metastases using tissue microarrays. Tumors with ≥50% cells showing positive membrane staining were considered to have high expression of PD-L1. RESULTS: PD-L1 expression of any intensity was identified in 32.8% of cases. High PD-L1 expression was found in 7.4% of NSCLC. Squamous cell carcinomas (8.1%) and large cell carcinomas (12.1%) showed high PD-L1 expression more commonly than adenocarcinomas (5.1%) but this was not statistically significant (p=0.072). High PD-L1 expression was associated with younger patient age and high tumor grade (p<0.05). There was no association with gender, tumor size, stage, nodal status, EGFR or KRAS mutation status. In multivariate analysis, patients with high PD-L1 expression had significantly longer overall survival (p<0.05). CONCLUSIONS: PD-L1 is expressed at high levels in a significant proportion of NSCLC and appears to be a favorable prognostic factor in early stage disease. As there are potential sampling limitations using tissue microarrays to assess heterogeneously expressed biomarkers, and as the results may differ in advanced stage disease, further studies are recommended.
OBJECTIVES: Immune checkpoint blockade using inhibitors of programmed death-1 have shown promise in early phase clinical trials in NSCLC and programmed death-ligand 1 (PD-L1) tumoral expression could potentially be a useful predictive marker. Data reporting the prevalence of PD-L1 expression in NSCLC and clinicopathologic associations is very limited. We sought to determine the frequency of PD-L1 expression in NSCLC and investigate associations with clinicopathologic features and patient outcome. MATERIALS AND METHODS:PD-L1 expression was analyzed using immunohistochemistry (Merck; clone 22C3) in 678 stages I-III NSCLC and 52 paired nodal metastases using tissue microarrays. Tumors with ≥50% cells showing positive membrane staining were considered to have high expression of PD-L1. RESULTS:PD-L1 expression of any intensity was identified in 32.8% of cases. High PD-L1 expression was found in 7.4% of NSCLC. Squamous cell carcinomas (8.1%) and large cell carcinomas (12.1%) showed high PD-L1 expression more commonly than adenocarcinomas (5.1%) but this was not statistically significant (p=0.072). High PD-L1 expression was associated with younger patient age and high tumor grade (p<0.05). There was no association with gender, tumor size, stage, nodal status, EGFR or KRAS mutation status. In multivariate analysis, patients with high PD-L1 expression had significantly longer overall survival (p<0.05). CONCLUSIONS:PD-L1 is expressed at high levels in a significant proportion of NSCLC and appears to be a favorable prognostic factor in early stage disease. As there are potential sampling limitations using tissue microarrays to assess heterogeneously expressed biomarkers, and as the results may differ in advanced stage disease, further studies are recommended.
Authors: Dwight Owen; Benjamin Chu; Amy M Lehman; Lakshmanan Annamalai; Jennifer H Yearley; Konstantin Shilo; Gregory A Otterson Journal: J Thorac Oncol Date: 2018-04-24 Impact factor: 15.609
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
Authors: Andreas H Scheel; Sascha Ansén; Anne M Schultheis; Matthias Scheffler; Rieke N Fischer; Sebastian Michels; Martin Hellmich; Julie George; Thomas Zander; Michael Brockmann; Erich Stoelben; Harry Groen; Wim Timens; Sven Perner; Michael von Bergwelt-Baildon; Reinhard Büttner; Jürgen Wolf Journal: Oncoimmunology Date: 2016-03-16 Impact factor: 8.110