CD 274 CD CD 274 ( PDL 1 PDL PDL 1 ) and JAK 2 JAK JAK 2 genomic amplifications in pulmonary squamous‐cell and adenocarcinoma patients

摘要

Aims CD 274 ( PDL 1 ) and JAK 2 (9p24.1) gene amplifications have been recently described in pulmonary carcinomas in association with programmed death‐ligand 1 ( PD ‐L1) expression. Furthermore, PTEN loss has been explored preclinically in relation to PD ‐L1 expression. Our aim was to determine whether these genomic alterations affect PD ‐L1 expression levels in non‐small‐cell lung cancer. Methods and results PD ‐L1 and PTEN expression determined by immunohistochemistry ( IHC ), and CD 274 , JAK 2 and PTEN copy number alterations ( CNA s) determined by fluorescence in‐situ hybridisation, were studied in 171 pulmonary carcinoma specimens. PD ‐L1 expression was positive in 40 cases (23.3%), and CD 274 amplification was present in 14 tumours (8.8%). Concordance between both events was found in 12 of 14 amplified cases ( P = 0.0001). We found nine JAK 2 ‐amplified cases (5.7%), seven with PD ‐L1 expression ( P = 0.0006). Moreover, six of the seven cases had JAK 2 and CD 274 coamplification (9p24.1 genomic amplification). Remarkably, the average PD ‐L1 IHC score was higher in these amplified cases (230 versus 80; P = 0.001). Non‐statistical associations were observed between PD ‐L1 expression and PTEN loss and PTEN deletions. Conclusions We describe a subset of patients (8.2%) who had 9p24.1 amplifications resulting in high expression of PD ‐L1. Our results provide evidence for genomic up‐regulation of PD ‐L1 expression in non‐small‐cell lung cancer.