• Keith M Kerr, Erik Thunnissen, Urania Dafni, Stephen P Finn, Lukas Bubendorf, Alex Soltermann, Eric Verbeken, Wojciech Biernat, Arne Warth, Antonio Marchetti, Speel Ernst-Jan M EM Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, Netherlands., Sarawati Pokharel, Anne Marie Quinn, Kim Monkhorst, Atilio Navarro, Line Bille Madsen, Teodora Radonic, Joan Wilson, Graziano De Luca, Steven G Gray, Richard Cheney, Spasenija Savic, Miguel Martorell, Thomas Muley, Paul Baas, Peter Meldgaard, Fiona Blackhall, Anne-Marie Dingemans, Rafal Dziadziuszko, Johan Vansteenkiste, Walter Weder, Varvara Polydoropoulou, Thomas Geiger, Roswitha Kammler, Solange Peters, Rolf Stahel, and Lungscape Consortium.
• Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom. Electronic address: k.kerr@abdn.ac.uk.
• Lung Cancer. 2019 May 1; 131: 95-103.

IntroductionThe PD-L1 biomarker is an important factor in selecting patients with non-small cell lung cancer for immunotherapy. While several reports suggest that PD-L1 positivity is linked to a poor prognosis, others suggest that PD-L1 positive status portends a good prognosis.MethodsPD-L1 positivity prevalence, assessed via immunohistochemistry (IHC) on tissue microarrays (TMAs), and its association with clinicopathological characteristics, molecular profiles and patient outcome- Relapse-free Survival (RFS), Time-to-Relapse (TTR) and Overall Survival (OS)- is explored in the ETOP Lungscape cohort of stage I-III non-small cell lung cancer (NSCLC). Tumors are considered positive if they have ≥1/5/25/50% neoplastic cell membrane staining.ResultsPD-L1 expression was assessed in 2182 NSCLC cases (2008 evaluable, median follow-up 4.8 years, 54.6% still alive), from 15 ETOP centers. Adenocarcinomas represent 50.9% of the cohort (squamous cell: 42.4%). Former smokers are 53.7% (current: 31.6%, never: 10.5%). PD-L1 positivity prevalence is present in more than one third of the Lungscape cohort (1%/5% cut-offs). It doesn't differ between adenocarcinomas and squamous cell histologies, but is more frequently detected in higher stages, never smokers, larger tumors (1/5/25% cut-offs). With ≥1% cut-off it is significantly associated with IHC MET overexpression, expression of PTEN, EGFR and KRAS mutation (only for adenocarcinoma). Results for 5%, 25% and 50% cut-offs were similar, with MET being significantly associated with PD-L1 positivity both for AC (p < 0.001, 5%/25%/50% cut-offs) and SCC (p < 0.001, 5% & 50% cut-offs and p = 0.0017 for 25%). When adjusting for clinicopathological characteristics, a significant prognostic effect was identified in adenocarcinomas (adjusted p-values: 0.024/0.064/0.063 for RFS/TTR/OS 1% cut-off, analogous for 5%/25%, but not for 50%). Similar results obtained for the model including all histologies, but no effect was found for the squamous cell carcinomas.ConclusionPD-L1 positivity, when adjusted for clinicopathological characteristics, is associated with a better prognosis for non-metastatic adenocarcinoma patients.Copyright © 2019 Elsevier B.V. All rights reserved.

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