Adam Szpechcinski1, Maciej Bryl2, Piotr Wojcik3, Grzegorz Czyzewicz4, Emil Wojda5, Piotr Rudzinski6, Katarzyna Duk7, Joanna Moes-Sosnowska7, Krystyna Maszkowska-Kopij8, Renata Langfort9, Aleksander Barinow-Wojewodzki2, Joanna Chorostowska-Wynimko7. 1. Department of Genetics and Clinical Immunology, National Tuberculosis and Lung Diseases Institute, Warsaw, Poland. Electronic address: a.szpechcinski@igichp.edu.pl. 2. Department of Oncology, E.J. Zeyland Wielkopolska Center of Pulmonology and Thoracic Surgery, Poznan, Poland. 3. Oncogene Diagnostics Sp. z o. o., Cracow, Poland. 4. Department of Oncology, The John Paul II Specialist Hospital, Cracow, Poland. 5. II Department of Lung Diseases, National Tuberculosis and Lung Diseases Institute, Warsaw, Poland. 6. Department of Surgery, National Tuberculosis and Lung Diseases Institute, Warsaw, Poland. 7. Department of Genetics and Clinical Immunology, National Tuberculosis and Lung Diseases Institute, Warsaw, Poland. 8. Outpatient Clinic, National Tuberculosis and Lung Diseases Institute, Warsaw, Poland. 9. Department of Pathomorphology, National Tuberculosis and Lung Diseases Institute, Warsaw, Poland.
Abstract
PURPOSE: The detection of epidermal growth factor receptor (EGFR) mutations in plasma cell-free DNA (cfDNA) is an auxiliary tool for the molecular diagnosis of non-small cell lung cancer (NSCLC), especially when an adequate tumor tissue specimen cannot be obtained. We compared the diagnostic accuracy of two commonly used in vitro diagnostic-certified allele-specific quantitative PCR assays for detecting plasma cfDNA EGFR mutations. METHODS: We analyzed EGFR mutations in plasma cfDNA from 90 NSCLC patients (stages I-IV) before treatment (n = 60) and after clinical progression on EGFR tyrosine kinase inhibitors (n = 30) using the cobas EGFR mutation test v2 (Roche Molecular Systems, Inc.) and therascreen EGFR Plasma RGQ PCR kit (Qiagen GmbH). RESULTS: There was higher concordance between plasma cfDNA and matched tumor tissue EGFR mutations with cobas (66.67%) compared with therascreen (55.93%). The concordance rate increased to 90.00% with cobas (Cohen's kappa coefficient, κ = 0.80; p < 0.0001) and 73.33% with therascreen (κ = 0.49; p = 0.0009) in advanced NSCLC patients. In treatment-naïve patients, cobas was superior to therascreen (sensitivity: 82.35% vs. 52.94%; specificity: 100% vs. 100%). In patients with clinical progression on EGFR tyrosine kinase inhibitors, EGFR exon 20 p.T790M was detected in 30% and 23% of cfDNA samples by cobas and therascreen, respectively. CONCLUSIONS: Cobas was superior to therascreen for detection of plasma EGFR mutations in advanced NSCLC. Plasma cfDNA EGFR mutation analysis is complex; therefore, the diagnostic accuracy of commercially available assays should be validated.
PURPOSE: The detection of epidermal growth factor receptor (EGFR) mutations in plasma cell-free DNA (cfDNA) is an auxiliary tool for the molecular diagnosis of non-small cell lung cancer (NSCLC), especially when an adequate tumor tissue specimen cannot be obtained. We compared the diagnostic accuracy of two commonly used in vitro diagnostic-certified allele-specific quantitative PCR assays for detecting plasma cfDNA EGFR mutations. METHODS: We analyzed EGFR mutations in plasma cfDNA from 90 NSCLC patients (stages I-IV) before treatment (n = 60) and after clinical progression on EGFR tyrosine kinase inhibitors (n = 30) using the cobas EGFR mutation test v2 (Roche Molecular Systems, Inc.) and therascreen EGFR Plasma RGQ PCR kit (Qiagen GmbH). RESULTS: There was higher concordance between plasma cfDNA and matched tumor tissue EGFR mutations with cobas (66.67%) compared with therascreen (55.93%). The concordance rate increased to 90.00% with cobas (Cohen's kappa coefficient, κ = 0.80; p < 0.0001) and 73.33% with therascreen (κ = 0.49; p = 0.0009) in advanced NSCLC patients. In treatment-naïve patients, cobas was superior to therascreen (sensitivity: 82.35% vs. 52.94%; specificity: 100% vs. 100%). In patients with clinical progression on EGFR tyrosine kinase inhibitors, EGFR exon 20 p.T790M was detected in 30% and 23% of cfDNA samples by cobas and therascreen, respectively. CONCLUSIONS: Cobas was superior to therascreen for detection of plasma EGFR mutations in advanced NSCLC. Plasma cfDNA EGFR mutation analysis is complex; therefore, the diagnostic accuracy of commercially available assays should be validated.
Authors: Hyunwoo Lee; Jin Hee Park; Joungho Han; Young Mog Shim; Jhingook Kim; Yong Soo Choi; Hong Kwan Kim; Jong Ho Cho; Yoon-La Choi; Wan-Seop Kim Journal: Cancers (Basel) Date: 2022-06-18 Impact factor: 6.575