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doi:10.1378/chest.06-1673
(Chest. 2007; 131:1628-1634)
© 2007 American College of Chest Physicians
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Detection of Epidermal Growth Factor Receptor Mutation in Transbronchial Needle Aspirates of Non-Small Cell Lung Cancer*

Atsushi Horiike, MD; Hideharu Kimura, MD, PhD; Kazuto Nishio, MD, PhD; Fumiyoshi Ohyanagi, MD, PhD; Yukitoshi Satoh, MD, PhD; Sakae Okumura, MD; Yuichi Ishikawa, MD, PhD; Ken Nakagawa, MD; Takeshi Horai, MD and Makoto Nishio, MD

* From the Thoracic Center (Drs. Horiike, Ohyanagi, Satoh, Okumura, Nakagawa, Horai, and Nishio) and Department of Pathology (Dr. Ishikawa), Cancer Institute Hospital, Japanese Foundation for Cancer Research; and Shien-Lab (Drs. Kimura and Nishio), National Cancer Center Hospital, Tokyo, Japan.

Correspondence to: Makoto Nishio, MD, Cancer Institute Hospital, Ariake 3–10-6, Koto-ku, 135-8550, Tokyo, Japan; e-mail: mnishio{at}jfcr.or.jp

Abstract

Background: Somatic mutations of epidermal growth factor receptor (EGFR) are closely associated with an objective response to EGFR tyrosine kinase inhibitors. However, it is difficult to obtain sufficient tumor samples from patients with non-small cell lung cancer (NSCLC), so these diagnoses are often made using cytology procedures alone. The aim of this study was to detect EGFR mutations in transbronchial needle aspiration (TBNA) samples using both direct sequencing and a highly sensitive assay (Scorpions Amplified Refractory Mutation System; DxS; Manchester, UK) [ARMS], and to compare the sensitivity of these methods.

Methods: We enrolled 94 patients (63 men and 31 women) with NSCLC in this study. Cytologic diagnoses were adenocarcinoma (n = 58), squamous cell carcinoma (n = 24), and other types of NSCLC (n = 12). We extracted DNA from the TBNA samples, and EGFR mutations were analyzed using both direct sequencing (exons 19 and 21) and the Scorpions ARMS method (E746 A750del and L858R).

Results: Mutations were detected in 31 patients (33%; 14 women and 17 men). Of these, 23 patients had adenocarcinoma, 4 had squamous cell carcinoma, and 4 had other types of NSCLC. Direct sequencing detected 13 mutations (14%) in 13 patients (E746-A750del, n = 6; L858R, n = 7), and the Scorpions ARMS method detected 27 mutations (29%) in 27 patients (E746 A750del, n = 16; L858R, n = 11 patients).

Conclusions: Both methods detected EGFR mutations in TBNA samples, but Scorpions ARMS is more sensitive than direct sequencing.

Key Words: epidermal growth factor receptor • epidermal growth factor receptor mutation • epidermal growth factor receptor tyrosine kinase inhibitor • Scorpions Amplified Refractory Mutation System • transbronchial needle aspiration


Related Editorial

Transbronchial Fine-Needle Aspiration, Epidermal Growth Factor Receptor Mutations, and the Scorpion’s Touch
Dani S. Zander
Chest 2007 131: 1619-1620. [Full Text] [PDF]



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D. S. Zander
Transbronchial Fine-Needle Aspiration, Epidermal Growth Factor Receptor Mutations, and the Scorpion's Touch
Chest, June 1, 2007; 131(6): 1619 - 1620.
[Full Text] [PDF]




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