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Updated: Aug 28, 2025
Using 22C3 Anti-PD-L1 Antibody Concentrate on Biopsy and Cytology Samples from Non-small Cell Lung Cancer Patients
Published on: September 25, 2018
Mutational Landscape and Expression of PD-L1 in Patients with Non-Small Cell Lung Cancer Harboring Genomic
Alessa Fischer1, Lorenz Bankel1, Stefanie Hiltbrunner1
1Department of Medical Oncology and Hematology, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland.
Background:
Mesenchymal-to-epithelial transition (MET) exon 14 skipping mutations and MET gene amplification occur in 3-5% of non-small cell lung cancer (NSCLC) patients. Tyrosine kinase inhibitors (TKIs) targeting MET alterations have shown promising results in these patients.
Objective:
The aim of this study was to describe the genomic profile, PD-L1 expression and clinicopathological features of MET dysregulated NSCLC.
Patients And Methods:
We identified 188 patients with advanced-stage NSCLC with data on MET expression by immunohistochemistry (IHC). IHC for PD-L1 expression was performed in 131 patient samples, and next-generation sequencing (NGS) analysis was performed in 109 patient samples.
Results:
MET exon 14 skipping alterations were identified in 16 (14.7%) samples, MET amplifications with cut-off ≥4 copy number variations were identified in 11 (10.1%) samples, and an oncogenic MET mutation (MET p.D1228N) was identified in 1 (0.9%) sample. 12/15 tumors (80.0%) harboring MET exon 14 alterations and 7/11 (63.6%) MET-amplified tumors expressed PD-L1 in ≥1% of tumor cells. Tumors harboring MET exon 14 skipping alterations expressed PD-L1 more frequently than MET wild-type IHC-positive tumors (p = 0.045). Twenty-five percent of MET exon 14-altered cases and 33% of MET-amplified cases harbored potentially targetable oncogenic co-mutations in KRAS, BRAF, and EGFR. The most frequent co-occurring mutations in all MET-altered tumors were TP53, KRAS, BRAF, and CDK4.
Conclusions:
We demonstrated that MET exon 14 skipping alterations and MET amplification are not mutually exclusive to other oncogenic co-mutations, and report the association of genomic MET alterations with PD-L1 expression. Since genomic MET alterations are emerging targets requiring upfront treatment, optimal understanding of the co-mutational landscape for this patient population is needed.
Insights
MET exon 14 skipping mutations and MET amplification impact non-small cell lung cancer (NSCLC). These MET alterations are associated with PD-L1 expression and co-occurring mutations, guiding future targeted therapies.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Mesenchymal-to-epithelial transition (MET) exon 14 skipping mutations and MET gene amplification affect 3-5% of non-small cell lung cancer (NSCLC) patients.
- Tyrosine kinase inhibitors (TKIs) targeting MET alterations show promise for these patients.
Purpose of the Study:
- To characterize the genomic profile, PD-L1 expression, and clinicopathological features of MET-dysregulated NSCLC.
- To investigate the co-mutational landscape in MET-altered NSCLC.
Main Methods:
- Analysis of 188 advanced-stage NSCLC patients.
- Immunohistochemistry (IHC) for MET and PD-L1 expression.
- Next-generation sequencing (NGS) for genomic alterations.
Main Results:
- MET exon 14 skipping alterations (14.7%) and MET amplification (10.1%) were identified.
- MET-altered tumors frequently expressed PD-L1 (80% for exon 14 skipping, 63.6% for amplification).
- Co-occurring oncogenic mutations in KRAS, BRAF, EGFR, TP53, and CDK4 were observed.
Conclusions:
- Genomic MET alterations are associated with PD-L1 expression and are not mutually exclusive to other oncogenic co-mutations.
- Understanding the co-mutational landscape of MET-altered NSCLC is crucial for upfront treatment strategies.
