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Lung Cancer. 2019 May;131:95-103. doi: 10.1016/j.lungcan.2019.03.012. Epub 2019 Mar 15.

A retrospective cohort study of PD-L1 prevalence, molecular associations and clinical outcomes in patients with NSCLC: Results from the European Thoracic Oncology Platform (ETOP) Lungscape Project.

Author information

1
Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom. Electronic address: k.kerr@abdn.ac.uk.
2
Department of Pathology, VU University Medical Center, Amsterdam, Netherlands.
3
Froniter Science Foundation-Hellas & University of Athens, Athens, Greece.
4
Department of Histopathology, St James's Hospital and Trinity College, Dublin, Ireland.
5
Institute of Pathology, University Hospital Basel, Basel, Switzerland.
6
Institute of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.
7
Department of Pathology, University Hospital KU Leuven, Leuven, Belgium.
8
Department of Pathomorphology, Medical University of Gdansk, Gdansk, Poland.
9
Department of Pathology, Universitätsklinikum Heidelberg, Heidelberg, Germany.
10
Center of Predicitve Predictive Molecular Medicine, CeSI, University of Chieti-Pescara, Chieti, Italy.
11
Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, Netherlands.
12
Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY, USA.
13
Wythenshawe Hospital, Department of Histopathology, Manchester University NHS Foundation Trust, Manchester, United Kingdom.
14
Division of Pathology, The Netherlands Cancer Institute, Amsterdam, Netherlands.
15
Department of Pathology, Consorcio Hospital General Universitario de Valencia, Valencia, Spain.
16
Department of Pathology, Aarhus University Hospital, Aarhus, Denmark.
17
Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom.
18
Department of Clinical Medicine, St James's Hospital and Trinity College Dublin, Dublin, Ireland.
19
Department of Pathology, State University of New York at Buffalo, Buffalo, NY, USA.
20
Translational Research Unit, Thoraxklinik, University Hospital of Heidelberg, and Translational Lung Research Center (TLRC) Heidelberg, German Center for Lung Research (DZL), Heidelberg, Germany.
21
Department of Thoracic Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands.
22
Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
23
Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom.
24
Department of Pulmonology, Maastricht University Medical Center, Maastricht, Netherlands.
25
Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland.
26
Department of Respiratory Oncology, University Hospital KU Leuven, Leuven, Belgium.
27
Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
28
Translational Research Coordination, ETOP Coordinating Office, Bern, Switzerland.
29
Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
30
Clinic of Oncology, University Hospital Zurich, Zurich, Switzerland.

Abstract

INTRODUCTION:

The 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.

METHODS:

PD-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.

RESULTS:

PD-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.

CONCLUSION:

PD-L1 positivity, when adjusted for clinicopathological characteristics, is associated with a better prognosis for non-metastatic adenocarcinoma patients.

KEYWORDS:

Non-small cell lung cancer; PD-L1

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