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

PDF  |  HTML  |  How to cite

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

Metrics: PDF 1908 views  |   HTML 4413 views  |   ?  


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: [email protected]

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 24455