CD274 (PDL1) and JAK2 genomic amplifications in pulmonary squamous-cell and adenocarcinoma patients

Abstract

Aims

CD274 (PDL1) and JAK2 (9p24.1) gene amplifications have been recently described in pulmonary carcinomas in association with PD-L1 protein expression. Also, PTEN loss have been explored preclinically in relation with PD-L1 expression. It remains to be determined if these genomic alterations may affect PD-L1 expression levels in non-small cell lung cancer.

Methods and results

PD-L1 and PTEN protein expression by IHC, and CD274, JAK2 and PTEN gene copy number alterations (CNAs) by FISH were studied in 171 pulmonary carcinoma specimens. PD-L1 expression was positive in 40 cases (23.3%) while CD274 gene amplification in 14 tumours (8.8%). Concordance between both events was found in 12 out of 14 amplified cases (p=0.0001). We found nine JAK2 amplified cases (5.7%), seven with PD-L1 expression (p=0.0006). Moreover, six out of the seven cases had both, JAK2 and CD274 co-amplification (9p24.1 genomic amplification). Remarkably, average PD-L1 IHC score was higher in these amplified cases (230 vs. 80; p=0.001). Non-statistical association were observed between PD-L1 expression and PTEN loss and PTEN deletions.

Conclusions

We described a subset of patients (8.2%) that 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.

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