Correlation of MET gene amplification and TP53 mutation with PD-L1 expression in non-small cell lung cancer

// Maher Albitar 1 , Sucha Sudarsanam 1 , Wanlong Ma 1 , Shiping Jiang 1 , Wayne Chen 1 , Vincent Funari 1 , Forrest Blocker 1 and Sally Agersborg 1 1 NeoGenomics Laboratories, Aliso Viejo, CA, USA Correspondence to: Maher Albitar, email: maher.albitar@neogenomics.com Keywords: NSCLC; PD-L1; EGFR; MET; TP53 Received: October 06, 2017     Accepted: January 09, 2018     Published: February 08, 2018 ABSTRACT Background: The role of MET amplification in lung cancer, particularly in relation to checkpoint inhibition and EGFR WT, has not been fully explored. In this study, we correlated PD-L1 expression with MET amplification and EGFR , KRAS , or TP53 mutation in primary lung cancer. Methods: In this retrospective study, tissue collected from 471 various tumors, including 397 lung cancers, was tested for MET amplification by FISH with a MET /centromere probe. PD-L1 expression was evaluated using clone SP142 and standard immunohistochemistry, and TP53 , KRAS , and EGFR 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 EGFR mutation (P=0.0003), and positively correlated with TP53 mutation (P=0.0001) and MET amplification (P=0.004). Patients with TP53 mutations had significantly higher MET amplification (P=0.007), and were more likely (P=0.0002) to be EGFR wild type. There was no correlation between KRAS mutation and overall PD-L1 expression, but significant positive correlation between PD-L1 expression and KRAS with TP53 co-mutation (P=0.0002). A cut-off for the ratio of MET : centromere signal was determined as 1.5%, and 4% of lung cancer patients were identified as MET amplified. Conclusions: This data suggests that in lung cancer both MET and TP53 play direct roles in regulating PD-L1 opposing EGFR . Moreover, KRAS and TP53 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.