4P - Co-amplifications of PD-L1/PD-L2 genes (9p24.1) and PD-L1 protein expression in NSCLC patients

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Poster lunch
Topics Thoracic malignancies
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter Sergi Clavé
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors S. Clavé1, D. Casadevall2, L. Pijuan1, M. Rodríguez-Rivera1, P. García-Moreno1, Á. Taus2, J. Albanell2, B. Espinet1, E. Arriola3, M. Salido1
  • 1Pathology Department, Hospital del Mar, 08003 - Barcelona/ES
  • 2Oncology Department, Hospital del Mar, 08003 - Barcelona/ES
  • 3Cancer Sciences Unit, Southampton General Hospital, SO16 6YD - Southampton/GB

Abstract

Background

Co-amplification of PD-L1 and PD-L2 genes on chromosome 9p24.1 has been suggested as a predictor of response to immune blockade treatment strategies with anti PD-1/PD-L1 agents. Recently, PD-L1 amplifications have been seen in ∼5% of NSCLC. We aimed to determine the prevalence of PD-L1 copy number alterations (CNAs) and the subsequent presence of ligand expression in NSCLC tumor cells.

Methods

We tested 75 NSCLC patients (67 adenocarcinomas and 8 squamous cell carcinomas (SCCs)) included in 5 TMAs for chromosome 9p24.1 (PD-L1 and PD-L2) CNAs by FISH (Zytovision) and for PD-L1 expression by IHC (#SP142 clone, Ventana). We collected clinical data together with EGFR and KRAS mutational status and ALK rearrangements.

Results

PD-L1/PD-L2 CNAs were found in 33 patients (44%): 5 gene co-amplifications (6.7%), 6 high polysomy cases (8%) and 22 cases with chromosome 9 trisomy (29.3%). All amplified cases presented also high PD-L1 expression, whereas only 2 of the high-polysomy cases showed increased protein expression. Samples without PD-L1/PD-L2 CNAs had completely negative PD-L1 expression. Among the 5 amplified cases, all patients were male, current of former smokers with a median age of 62 years (range: 53–72) and 3 of them with acinar/solid adenocarcinoma histology. Remarkably, 2 cases had SCCs histology (p = 0.035) and 3 of them also harbored KRAS mutations (p = 0.021).

Conclusions

PD-L1/PD-L2 amplifications correlate with PD-L1 receptor expression in NSCLC. These alterations might be more commonly associated with SCC histology and KRAS mutations. The predictive and prognostic roles of PD-L1 FISH CNAs analysis should be further investigated.

Clinical trial identification

Legal entity responsible for the study

Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain

Funding

Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain

Disclosure

All authors have declared no conflicts of interest.