Oncotarget

Research Papers:

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

Maher Albitar _, Sucha Sudarsanam, Wanlong Ma, Shiping Jiang, Wayne Chen, Vincent Funari, Forrest Blocker and Sally Agersborg

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Oncotarget. 2018; 9:13682-13693. https://doi.org/10.18632/oncotarget.24455

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Abstract

Maher Albitar1, Sucha Sudarsanam1, Wanlong Ma1, Shiping Jiang1, Wayne Chen1, Vincent Funari1, Forrest Blocker1 and Sally Agersborg1

1NeoGenomics 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.


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