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Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
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PD-L1 gene amplification and focality: relationship with protein expression
Denis Leonardo Jardim1, Karthikeyan Murugesan2,3, Julia A Elvin3
1Centro de Oncologia, Hospital Sírio-Libanês, Sao Paulo, Brazil jardimde@gmail.com.
Journal for Immunotherapy of Cancer
|February 27, 2023
Summary
PD-L1 (CD274) amplification in tumors impacts protein expression, with focal amplifications correlating to higher PD-L1 levels. Understanding amplification level and focality is key for predicting immunotherapy response.
Area of Science:
- Oncology
- Genomics
- Immunotherapy
Background:
- Programmed death-ligand 1 (PD-L1) amplification is observed in a subset of malignancies.
- PD-L1 amplification may predict response to anti-PD-1/PD-L1 immunotherapy.
Purpose of the Study:
- To investigate how both copy number (CN) and focality of PD-L1 amplifications affect PD-L1 protein expression.
- To correlate PD-L1 CN alterations with PD-L1 protein levels via immunohistochemistry (IHC).
Main Methods:
- Analysis of 60,793 solid tumors undergoing comprehensive genomic profiling.
- Detection of PD-L1 CN alterations using a comparative genomic hybridization-like method.
- Correlation of PD-L1 CN changes with PD-L1 protein expression (DAKO 22C3 antibody) by IHC.
Main Results:
- 1.21% of tumors exhibited PD-L1 amplification (CD274 CN ≥ specimen ploidy +4).
- Highly focal amplifications (<0.1 mB) correlated with significantly higher PD-L1 IHC expression (median TPS 87.5% for ploidy ≥+4).
- Non-focal amplifications (≥20 mB) less frequently showed high PD-L1 expression, but could still present with high TPS.
Conclusions:
- PD-L1 protein expression is influenced by both the level and focality of PD-L1 amplification.
- Further research correlating amplification, focality, protein expression, and therapeutic outcomes is warranted.
