Comparison of epidermal growth factor receptor mutation statuses in tissue and plasma in stage I-IV non-small cell lung cancer patients
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Xiao Zhao1, Ru-Bing Han, Jing Zhao
1Department of Respiratory Diseases, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Peking University, Beijing, China.
Background:
Epidermal growth factor receptor (EGFR) mutations play essential roles in the treatment of non-small cell lung cancer (NSCLC) patients using EGFR tyrosine kinase inhibitors. Detection of EGFR mutations in blood cell-free DNA (cfDNA) seems promising. However, the mutation status in the plasma/serum is not always consistent with that in the tissues.
Objectives:
The aims of this study were to compare the mutation statuses in plasma to those in tissues and thus to determine the specific subgroups of NSCLC patients who may be the best candidates for EGFR mutation analyses using blood cfDNA.
Methods:
A total of 111 pairs of tissue and plasma samples were collected. Mutant-enriched PCR and sequencing analyses were performed to detect EGFR exon 19 deletions and exon 21 L858R mutations.
Results:
Mutations were discovered in 43.2% (48/111) of the patients. The overall rate of consistency of the EGFR mutation statuses for the 111 paired plasma and tissue samples was 71.2% (79/111). The sensitivity and specificity rates of detecting EGFR mutations in the plasma were 35.6% (16/45) and 95.5% (63/66), respectively. The disease stage and tumor differentiation subgroups showed significantly different detection sensitivities; the sensitivity was 10% in early-stage patients and 56% in advanced-stage patients (p = 0.0014). For patients with poorly differentiated tumors, the sensitivity was 77.8%, which was significantly different from those with highly differentiated (20%; p = 0.0230) and moderately differentiated tumors (19%; p = 0.0042).
Conclusion:
Blood analyses for EGFR mutations may be effectively used in advanced-stage patients or patients with poorly differentiated tumors.
Insights
Blood tests for epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) are most effective for advanced-stage or poorly differentiated tumors. This study compared plasma cfDNA EGFR mutation status to tissue, identifying patient subgroups for optimal liquid biopsy use.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- Epidermal growth factor receptor (EGFR) mutations are crucial for targeted therapy in non-small cell lung cancer (NSCLC) using tyrosine kinase inhibitors.
- Detecting EGFR mutations in circulating cell-free DNA (cfDNA) from blood offers a promising, less invasive approach.
- However, discrepancies between plasma and tissue EGFR mutation status necessitate identifying optimal patient subgroups for blood-based testing.
Purpose of the Study:
- To directly compare EGFR mutation detection in plasma cfDNA versus tumor tissue in NSCLC patients.
- To determine specific NSCLC patient subgroups who are best candidates for EGFR mutation analysis using blood cfDNA.
Main Methods:
- Analysis of 111 paired tissue and plasma samples from NSCLC patients.
- Utilized mutant-enriched PCR and sequencing to detect common EGFR mutations (exon 19 deletions and exon 21 L858R).
Main Results:
- Overall agreement between plasma and tissue EGFR mutation status was 71.2%.
- Plasma detection sensitivity was 35.6% and specificity was 95.5%.
- Detection sensitivity was significantly higher in advanced-stage (56%) vs. early-stage (10%) and poorly differentiated tumors (77.8%) vs. well-differentiated tumors (20%).
Conclusions:
- Blood-based EGFR mutation analysis is most effective for advanced-stage NSCLC patients.
- Liquid biopsies show higher sensitivity in NSCLC patients with poorly differentiated tumors.
- These findings help refine patient selection for cfDNA-based EGFR mutation testing.
