Concordance of Epidermal Growth Factor Receptor Mutation from Tissue Biopsy and Plasma Circulating Tumor DNA in Treatment-Naïve Lung Adenocarcinoma Patients

Authors

  • Noni Novisari Soeroso Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Sumatera Utara, Universitas Sumatera Utara Hospital, Medan, Indonesia
  • Hendra Taufik Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Sumatera Utara, Universitas Sumatera Utara Hospital, Medan, Indonesia
  • Setia Putra Tarigan Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Sumatera Utara, Universitas Sumatera Utara Hospital, Medan, Indonesia
  • Erna Mutiara Department of Biostatistic, Faculty of Public Health, Universitas Sumatera Utara, Medan, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2022.9275

Keywords:

Plasma circulating tumor DNA, Epidermal growth factor receptor mutation, Liquid biopsy, Lung cancer, Lung adenocarcinoma

Abstract

Background: Prevalence of Epidermal Growth Factor Receptor (EGFR) mutation in ctDNA in treatment-naïve individuals are not well established in Indonesia. In recent years, ctDNA as a specific and sensitive blood-based biomarker had been developed to detect the mutation. The study was done to understand the concordance and acceptance levels of ctDNA in detecting the gene mutation in lung adenocarcinoma patients.   

Methods: This study used cross-sectional approach with purposive sampling design in 100 treatment-naïve NSCLC, adenocarcinoma patients. Samples were obtained from bronchoscopy, and blood, which were examined to detect the mutation in formalin-fixed, paraffin-embedded (FFPE) specimens or plasma samples using QIAampDNA Micro Kit. Mutation was calculated by droplet digital PCR (ddPCR).  

Results: A hundred subjects with primary tumor tissue samples were compared with the plasma samples and mutation was detected in 20 patients (20.0%), 12 (12.0%) on exon 19, 7 (7.0%) on exon 21 and 1 (1.0%) on both exon 19 and 21. Within the plasma samples, mutation was found in 15 patients (15%) with mutation on exon 19 and 21 in 12 (12.0%) and 3 (3.0%) patients, respectively.  Within the two samples, concordance of EGFR mutation was 83.0% (83/100, P<0.001; correlation index: 0.42). Assuming presence of mutation as the benchmark, the accuracy of mutation presence in plasma DNA was 60.0% (9/15). Kappa test showed a weak agreement between the mutation in tissues and plasma, with a coefficient of 0.414 (95% CI).  

Conclusion: Tissue biopsy was still considered as the main option to detect EGFR mutation in lung cancer. More research on ctDNA as the standardized tools to detect the mutation are required.   

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References

Kemenkes RI, Pedoman Nasional Pelayanan Kanker 2014. Jakarta. Available from: http://www.kanker.kemkes.go.id/guidelines_read.php?id=1&cancer=4 [Last accessed on 2017 Oct 12].

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87-108. https://doi.org/10.3322/caac.21262 PMid:25651787 DOI: https://doi.org/10.3322/caac.21262

Hirsch FR, Scagliotti GV, Mulshine JL, Kwon R, Curran WJ, Wu Y, et al. Lung cancer: Current therapies and new targeted treatments. Lancet. 2016;6736:1-13. https://doi.org/10.1016/S0140-6736(16)30958-8 PMid:27574741 DOI: https://doi.org/10.1016/S0140-6736(16)30958-8

Chen Z, Fillmore CM, Hammerman PS, Kim CF, Wong KK. Non-small-cell lungcancers: A heterogeneous set of diseases. Nat Rev Cancer. 2014;14:535-46. https://doi.org/10.1038/nrc3775 PMid:25056707 DOI: https://doi.org/10.1038/nrc3775

Lindeman NI, Cagle PT, Aisner DL, Arcila ME, Beasley MB, Bernicker EH, et al. Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: Guideline from the college of american pathologists, the international association for the study of lung cancer, and the association for molecular pathology. Arch Pathol Lab Med. 2018;142:3:321-46. https://doi.org/10.5858/arpa.2017-0388-CP PMid:29355391 DOI: https://doi.org/10.5858/arpa.2017-0388-CP

Syahruddin E, Wulandari L, Muktiati NS, Rima A, Soeroso N, Ermayanti S, Levi M, et al. Uncommon EGFR mutations in cytological specimens of 1,874 newly diagnosed indonesian lung cancer patients. Lung Cancer. 2018;9:25-34. https://doi.org/10.2147/LCTT.S154116 PMid:29615847 DOI: https://doi.org/10.2147/LCTT.S154116

Soeroso NN, Ananda FR, Pradana A, Tarigan SP, Syahruddin E, Noor DR. The Absence of mutations in the Exon 2 KRAS Gene in Several Ethnic Groups in North Sumatra may not the main factor for lung cancer. Acta Inform Med. 2021;29(2):108-12. https://doi.org/10.5455/aim.2021.29.108-112 PMid:34584333 DOI: https://doi.org/10.5455/aim.2021.29.108-112

Herbreteau G, Vallee A, Charpentier S, Normanno N, Hofman P, Denis MG. Circulating free tumor DNA in non-small cell lung cancer (NSCLC): Clinical application and future perspectives. J Thorac Dis. 2019;11(1):S113-26. https://doi.org/10.21037/jtd.2018.12.18 PMid:30775034 DOI: https://doi.org/10.21037/jtd.2018.12.18

Douillard JY, Ostoros G, Cobo M, Ciuleanu T, McCormack R, Webster A, et al. First-line gefitinib in Cau-casian EGFR mutation-positive NSCLC patients: A phase-IV, open-label, single-arm study. Br J Cancer. 2014;110(1):55-62. https://doi.org/10.1038/bjc.2013.721 PMid:24263064 DOI: https://doi.org/10.1038/bjc.2013.721

Redig AJ, Costa DB, Taibi M, Boucher D, Johnson BE, Janne PA, et al. Prospective study of repeated biopsy feasibility and acquired resistance at disease progression in patients with advanced EGFR mutant lung cancer treated with erlotinib in a phase 2 trial. JAMA Oncol. 2016;2(9):1240-2. https://doi.org/10.1001/jamaoncol.2016.1304 PMid:27387964 DOI: https://doi.org/10.1001/jamaoncol.2016.1304

Sacher AG, Komatsubara KM, Oxnard GR. Application of plasma genotyping technologies in non-small cell lung cancer: A practical review. J Thorac Oncol. 2017;12(9):1344-56. https://doi.org/10.1016/j.jtho.2017.05.022 PMid:28611011 DOI: https://doi.org/10.1016/j.jtho.2017.05.022

Jahr S, Hentze H, Englisch S, Hardt D, Fackelmayer FO, Hesch RD, et al. DNA fragments in the blood plasma of cancer patients: Quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res. 2001;61(4):1659-65. PMid:11245480

Stroun M, Lyautey J, Lederrey C, Olson-Sand A, Anker P. About the possible origin and mechanism of circulating DNA apoptosis and active DNA release. Clin Chim Acta. 2001;313(1-2):139-42. PMid:11694251 DOI: https://doi.org/10.1016/S0009-8981(01)00665-9

Cho MS, Park CH, Lee S, Park HS. Clinicopathological parameters for circulating tumor DNA shedding in surgically resected non-small cell lung cancer with EGFR or KRAS mutation. PLoS One. 2020;15(3):e0230622. https://doi.org/10.1371/journal.pone.0230622 PMid:32196518 DOI: https://doi.org/10.1371/journal.pone.0230622

Soeroso NN, Zain-Hamid R, Sinaga BY, Sadewa AH, Syafiuddin T, Syahruddin E, et al. Genetic polymorphism of CYP2A6 and its relationship with nicotine metabolism in male bataknese smokers suffered from lung cancer in Indonesia. Open Access Maced J Med Sci. 2018;6(7):1199-205. https://doi.org/10.3889/oamjms.2018.259 PMid:30087722 DOI: https://doi.org/10.3889/oamjms.2018.259

Soeroso NN, Zain-Hamid R, Sinaga BY, Sadewa AH, Syafiuddin T, Syahruddin E, et al. The role of CYP2A6 genetic polymorphism in nicotine dependence and tobacco consumption among bataknese male smokers. Open Access Maced J Med Sci. 2018;6(5):864-6. https://doi.org/10.3889/oamjms.2018.224 PMid:29875862 DOI: https://doi.org/10.3889/oamjms.2018.224

Tarigan SP, Soeroso NN, Tumanggor CA, Gani S, Pradana A. Clinical profile of male patients with non-small cell lung cancer in Adam Malik General Hospital, Medan, Indonesia. Open Access Maced J Med Sci. 2019;7(16):2612-4. https://doi.org/10.3889/oamjms.2019.404 PMid:31777616 DOI: https://doi.org/10.3889/oamjms.2019.404

Soeroso NN, Tarigan SP, Saragih W, Sari ND, Lubis N, Lubis H. Lung adenocarcinoma presenting with an orbital metastasis. Respir Med Case Rep. 2018;25:116-8. https://doi.org/10.1016/j.rmcr.2018.08.005 PMid:30112271 DOI: https://doi.org/10.1016/j.rmcr.2018.08.005

Soeroso NN, Tanjung MF, Afiani D, Pradana A, Tarigan SP, Wahyuni AS. Procalcitonin level in non-small cell lung cancer patients among Indonesia population. Open Access Maced J Med Sci. 2018;6(11):2123-7. https://doi.org/10.3889.2018.421 PMid:30559873 DOI: https://doi.org/10.3889/oamjms.2018.421

Won YW, Han JY, Lee GK, Park SY, Lim KY, Yoon KA, et al. Comparison of clinical outcome of patients with non-small-cell lung cancer harbouring epidermal growth factor receptor exon 19 or exon 21 mutation. J Clin Pathol. 2011;64(11):947-52. https://doi.org/10.1136/jclinpath-2011-200169 PMid:21725039 DOI: https://doi.org/10.1136/jclinpath-2011-200169

Huang Z, Wang Z, Bai H, Wu M, An T, Zhao J, et al. The detection of EGFR mutation status in plasma is reproducible and can dynamically predict the efficacy of EGFR-TKI. Thoracic Cancer. 2012;3(4):334-40. https://doi.org/10.1111/j.1759-7714.2012.00133.x PMid:28920271 DOI: https://doi.org/10.1111/j.1759-7714.2012.00133.x

Goto K, Ichinose Y, Ohe Y, Yamamoto N, Negoro S, Nishio K, et al. Epidermal growth factor receptor mutation in circulating free DNA in serum: From IPASS, a phase III study of gefitinib or carboplatin/paclitaxel in non-small cell lung cancer. J Thorac Oncol, 2012;7(1):115-21. https://doi.org/10.1097/JTO.0b013e3182307f98 PMid:21900837 DOI: https://doi.org/10.1097/JTO.0b013e3182307f98

Reck M, Hagiwara K, Han B, Tjulandin S, Grohé C, Yokoi T, et al. ctDNA determination of EGFR mutation status in European and Japanese patients with advanced NSCLC: The ASSESS study. J Thorac Oncol. 2016;11:1682-9. https://doi.org/10.1016/j.jtho.2016.05.036 PMid:27468938 DOI: https://doi.org/10.1016/j.jtho.2016.05.036

Wang S, Han X, Hu X, Wang X, Zhao L, Tang L, et al. Clinical significance of pretreatment plasma biomarkers in advanced non-small cell lung cancer patients. Clin Chim Acta. 2014;430:63-70. https://doi.org/10.1016/j.cca.2013.12.026 PMid:24378285 DOI: https://doi.org/10.1016/j.cca.2013.12.026

Douillard JY, Ostoros G, Cobo M, Ciuleanu T, Cole R, McWalter G, et al. Gefitinib treatment in EGFR mutated caucasian NSCLC: Circulating-free tumor DNA as a surrogate for determination of EGFR status. J Thorac Oncol. 2014;9(9):1345-53. https://doi.org/10.1097/JTO.0000000000000263 PMid:25122430 DOI: https://doi.org/10.1097/JTO.0000000000000263

Bai H, Mao L, Wang HS, Zhao J, Yang L, An TT, et al. Epidermal growth factor receptor mutations in plasma DNA samples predict tumor response in Chinese patients with stages IIIB to IV non-small-cell lung cancer. J Clin Oncol. 2009;27(16):2653-9. https://doi.org/10.1200/JCO.2008.17.3930 PMid:19414683 DOI: https://doi.org/10.1200/JCO.2008.17.3930

Zhao X, Han RB, Zhao J, Wang J, Yang F, Zhong W, et al. Comparison of epidermal growth factor receptor mutation statuses in tissue and plasma in stage I-IV non-small cell lung cancer patients. Respiration. 2013;85(2):119-25. https://doi.org/10.1159/000338790 PMid:22797485 DOI: https://doi.org/10.1159/000338790

Diaz LA Jr., Bardelli A. Liquid biopsies: Genotyping circulating tumor DNA. J Clin Oncol. 2014;32(6):579-86. https://doi.org/10.1200/JCO.2012.45.2011 PMid:24449238 DOI: https://doi.org/10.1200/JCO.2012.45.2011

Marchetti A, Normanno N, Pinto C, Taddei GL, Adamo V, Ardizzoni A, et al. Recommendations for mutational analysis of EGFR in lung carcinoma. Pathologica. 2010;102(3):119-26. PMid:21171518

Arriola E, Paredes-Lario A, García-Gomez R, Diz-Tain P, Constenla M, García-Girón C, et al. Comparison of plasma ctDNA and tissue/cytology-based techniques for the detection of EGFR mutation status in advanced NSCLC: Spanish data subset from ASSESS. Clin Transl Oncol. 2018;20(10):1261-7. https://doi.org/10.1007/s12094-018-1855-y PMid:29623586 DOI: https://doi.org/10.1007/s12094-018-1855-y

Zhang S, Zhu L, Chen X, Zhang X, Chen E, Fang H, et al. ctDNA assessment of EGFR mutation status in Chinese patients with advanced non-small cell lung cancer in real-world setting. J Thorac Dis. 2018;10(7):4169-77. https://doi.org/10.21037/jtd.2018.06.166 PMid:30174861 DOI: https://doi.org/10.21037/jtd.2018.06.166

Han B, Tjulandin S, Hagiwara K, Normanno N, Wulandari L, Laktionov K, et al. EGFR mutation prevalence in Asia-Pacific and Russian patients with advanced NSCLC of adenocarcinoma and non-adenocarcinoma histology: The IGNITE study. Lung Cancer. 2017;113:37-44. https://doi.org/10.1016/j.lungcan.2017.08.021 PMid:29110846 DOI: https://doi.org/10.1016/j.lungcan.2017.08.021

Park S, Olsen S, Ku BM, Lee MS, Jung HA, Sun JM, et al. High concordance of actionable genomic alterations identified between circulating tumor DNA-based and tissue-based next-generation sequencing testing in advanced non-small cell lung cancer: The Korean lung liquid versus invasive biopsy program. Cancer. 2021;127(16):3019-28. https://doi.org/10.1002/cncr.33571 PMid:33826761 DOI: https://doi.org/10.1002/cncr.33571

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Published

2022-03-25

How to Cite

1.
Soeroso NN, Taufik H, Tarigan SP, Mutiara E. Concordance of Epidermal Growth Factor Receptor Mutation from Tissue Biopsy and Plasma Circulating Tumor DNA in Treatment-Naïve Lung Adenocarcinoma Patients. Open Access Maced J Med Sci [Internet]. 2022 Mar. 25 [cited 2024 Feb. 23];10(T7):164-9. Available from: https://oamjms.eu/index.php/mjms/article/view/9275

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