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Original Research: LUNG CANCER |

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; Makoto Nishio, MD
Author and Funding Information

*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@jfcr.or.jp



Chest. 2007;131(6):1628-1634. doi:10.1378/chest.06-1673
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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.

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