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Journal of Thoracic Oncology:
doi: 10.1097/JTO.0000000000000041
Original Articles

Clinical Characteristics and Treatment Outcomes of Lung Adenocarcinomas with Discrepant EGFR Mutation Testing Results Derived from PCR-Direct Sequencing and Real-Time PCR-Based Assays

Chiu, Chao-Hua MD*,†‡; Ho, Hsiang-Ling PhD§; Chiang, Chi-Lu MD; Lin, Shiou-Fu MD; Ma, Hsiu-Hsun MS§; Chuang, Yu-Ting MS§; Lin, Kun-Yang MS§; Tsai, Chun-Ming MD†‡; Chou, Teh-Ying MD, PhD

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Abstract

Introduction:

Detection of epidermal growth factor receptor (EGFR) mutation has become the most critical molecular test in managing patients with advanced lung adenocarcinoma. Whether patients with discrepant EGFR mutation results determined by low- and high-sensitivity methods have different clinical outcomes with EGFR tyrosine kinase inhibitor (TKI) treatment needs to be further evaluated.

Methods:

Genomic DNA from serial lung adenocarcinoma samples that were EGFR wild-type determined by direct sequencing (DS) were reanalyzed using Scorpion/Amplification Refractory Mutation System (ARMS). The outcomes with EGFR-TKI treatment among patients with discrepant EGFR mutation results between DS and Scorpion/ARMS versus patients with EGFR mutations detected by DS were studied.

Results:

Of the 130 tumors studied, 28 (21.5%) were found to have EGFR mutations by Scorpion/ARMS. Discrepant EGFR mutation testing results were more common in samples from nonsmokers than in samples from smokers (30.7% versus 9.1%; p = 0.003) and in pleural than in nonpleural samples (62.5% versus 18.9%; p = 0.012). There was no significant difference in the abundance of cancer cells in region(s) selected for testing (26.2% in tumor cell percentage ≤50 versus 16.9% in tumor cell percentage >50; p = 0.201). During EGFR-TKI treatment, the progression-free survival in patients with discrepant EGFR mutation results was similar to those with EGFR mutations detected by DS (median, 13.4 versus 10.9 months; p = 0.225).

Conclusions:

DS overlooked EGFR mutation in a significant number of lung adenocarcinoma patients. These patients could have obtained the same benefit from EGFR-TKI when a high-sensitivity method such as Scorpion/ARMS was applied.

Copyright © 2013 by the International Association for the Study of Lung Cancer

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