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Comparison of detection methods of EGFR T790M mutations using plasma, serum, and tumor tissue in EGFR-TKI-resistant non-small cell lung cancer

Authors Kobayashi K, Naoki K, Manabe T, Masuzawa K, Hasegawa H, Yasuda H, Kawada I, Soejima K, Betsuyaku T

Received 6 January 2018

Accepted for publication 6 April 2018

Published 6 June 2018 Volume 2018:11 Pages 3335—3343

DOI https://doi.org/10.2147/OTT.S161745

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 4

Editor who approved publication: Dr Tohru Yamada


Keigo Kobayashi,1 Katsuhiko Naoki,1,2 Tadashi Manabe,1 Keita Masuzawa,1 Hanako Hasegawa,1 Hiroyuki Yasuda,1 Ichiro Kawada,1 Kenzo Soejima,1 Tomoko Betsuyaku1

1Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan; 2Department of Respiratory Medicine, Kitasato University School of Medicine, Kanagawa, Japan

Background: Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor, exerts remarkable effects against EGFR T790M resistance mutation-positive non-small cell lung cancer. Identifying T790M mutation by re-biopsy is essential before prescribing osimertinib. Tissue biopsy is the golden standard for this purpose, but several factors limit its success rate. The liquid biopsy with blood, using circulating tumor DNA, has been an alternative method. However, the true biological meaning and equivalence of liquid biopsy and tumor biopsy are still under investigation. Especially, the usefulness of serum samples to detect T790M mutation is not yet been known.
Patients and methods: We prospectively evaluated the sensitivity, specificity, and parallelism of the detection of EGFR mutations in tissue re-biopsy and liquid biopsy (plasma and serum), simultaneously, from June 2016 to May 2017. EGFR mutations in tumor re-biopsy were evaluated by COBAS ver2 and PNA-LNA PCR clamp method, and those in liquid biopsy were evaluated with COBAS ver2.
Results: Fifteen patients were enrolled. In 10 patients whose EGFR mutation was detected in liquid biopsy, the original EGFR mutation (exon 19 del or L858R) was detected in all patients. Detection of EGFR mutation by COBAS ver2 and by PNA-LNA method was almost the same in tissue re-biopsy. The detection rate of T790M was lower than that of the original EGFR mutation in liquid biopsy compared to that in tissue re-biopsy. The detection of T790M in serum exhibited a higher specificity (67%) and positive predictive value (50%) than that in plasma (50% and 40%, respectively). The detection sensitivity was similar in plasma and serum.
Conclusion: Plasma, serum, and tissue genotyping can have complementary roles for detecting EGFR-T790M using COBAS ver2. Repeated tests with different samples and different methods may improve accuracy of T790M detection and will lead to the maximum benefit for the patient.

Keywords: EGFR, T790M mutation, liquid biopsy, COBAS ver2, PNA-LNA PCR clamp method, osimertinib

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