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KMID : 0882420110810050611
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Korean Journal of Medicine
2011 Volume.81 No. 5 p.611 ~ p.622
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Predicting the Treatment Response Using a Direct Sequencing Method for EGFR in Non-Squamous, Non-Small Cell Lung Cancer
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Park Ji-Young
Jang Seung-Ho
Kim Hyo-Jung
Park Yong-Bum
Kwon Jung-Hye
Song Hun-Ho
Lee Kyung-Wha
Kim Jin-Hee
Kim Joo-Hee
Park Sung-Hoon
Hwang Yong-Il
Kim Dong-Kyu
Jung Ki-Suck
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Abstract
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Background/Aims:Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancers (NSCLCs) have emerged as a key predictive biomarker for EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment and should be the primary standard for selecting patients for first-line treatment with EGFR-TKIs. This retrospective study evaluated the ability of direct DNA sequencing to predict the EGFR-TKI response.
Methods:We sequenced exons 18-21 of the EGFR tyrosine kinase domain from genomic DNA isolated from 122 NSCLCs, using paraffin-embedded tissues or cytological specimens. Mutation status was compared with clinicopathological features. Clinical outcomes were assessed based on EGFR genotypes.
Results:EGFR gene mutations were identified in 36 patients. EGFR mutations were significantly more frequent in non-smokers or light smokers than in heavy smokers (44.8% vs. 10.9%, p < 0.001) and in females than in males (41.8% vs. 19.4%, p = 0.007). The response rate to EGFR-TKIs in patients with an EGFR mutation was 42.1% (8/19), in contrast to 18.9% (7/37) in patients without a mutation (p = 0.064). Patients with an EGFR mutation had significantly prolonged progression-free survival (8.5 vs. 1.5 months; p = 0.003) and overall survival (40.0 vs. 13.3 months; p = 0.006) with EGFR-TKI treatment, compared with patients without a mutation. Among the 15 patients who responded to EGFR-TKIs, 46.7% (7/15) had wild-type EGFR by the direct sequencing method.
Conclusions:EGFR-TKIs conferred substantial clinical benefit in patients with NSCLCs and EGFR mutations. Detection of an EGFR mutation currently relies on direct sequencing, which cannot be performed on small diagnostic specimens, and the method lacks sensitivity. Sensitive assays are needed to detect EGFR mutations in routine clinical samples.
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KEYWORD
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Carcinoma, Non-small cell lung, Receptor, Epidermal Growth Factor, Tyrosine Kinase Inhibitor, Sequence Analysis
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