Correlation of gene amplification and mutation with PD-L1 expression in non-small cell lung cancer.

Background: The role of amplification in lung cancer, particularly in relation to checkpoint inhibition and WT, has not been fully explored. In this study, we correlated PD-L1 expression with amplification and , , or mutation in primary lung cancer.

Methods: In this retrospective study, tissue collected from 471 various tumors, including 397 lung cancers, was tested for amplification by FISH with a /centromere probe. PD-L1 expression was evaluated using clone SP142 and standard immunohistochemistry, and , , and mutations were tested using next generation sequencing.

Results: Our results revealed that PD-L1 expression in non-small cell lung cancer is inversely correlated with mutation (P=0.0003), and positively correlated with mutation (P=0.0001) and amplification (P=0.004). Patients with mutations had significantly higher amplification (P=0.007), and were more likely (P=0.0002) to be wild type. There was no correlation between mutation and overall PD-L1 expression, but significant positive correlation between PD-L1 expression and with co-mutation (P=0.0002). A cut-off for the ratio of : centromere signal was determined as 1.5%, and 4% of lung cancer patients were identified as amplified.

Conclusions: This data suggests that in lung cancer both and play direct roles in regulating PD-L1 opposing . Moreover, and co-mutation may cooperate to drive PD-L1 expression in lung cancer. Adding MET or TP53 inhibitors to checkpoint inhibitors may be an attractive combination therapy in patients with lung cancer and MET amplification.