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Original Research: LUNG CANCER |

Assessment of Epidermal Growth Factor Receptor Mutation by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration*

Takahiro Nakajima, MD; Kazuhiro Yasufuku, MD, PhD, FCCP; Makoto Suzuki, MD, PhD; Kenzo Hiroshima, MD, PhD; Rieko Kubo, MS; Sherif Mohammed, MD; Yohei Miyagi, MD, PhD; Shoichi Matsukuma, PhD; Yasuo Sekine, MD, PhD; Takehiko Fujisawa, MD, PhD
Author and Funding Information

*From the Departments of Thoracic Surgery (Drs. Nakajima, Yasufuku, Suzuki, Mohammed, Sekine, and Fujisawa, and Ms. Kubo) and Diagnostic Pathology (Dr. Hiroshima), Graduate School of Medicine, Chiba University, Chiba, Japan; and the Division of Molecular Pathology and Genetics (Drs. Miyagi and Matsukuma), Kanagawa Cancer Center Research Institute, Kanagawa, Japan.

Correspondence to: Takehiko Fujisawa, MD, PhD, Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan; e-mail: fujisawat@faculty.chiba-u.jp



Chest. 2007;132(2):597-602. doi:10.1378/chest.07-0095
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Background: The presence of somatic mutations in epidermal growth factor receptor (EGFR) predicts the effectiveness of EGFR tyrosine kinase inhibitors (TKIs). It would be ideal if an EGFR mutation could be detected in biopsy samples, since the majority of non-small cell lung cancer patients are inoperable at the time of presentation. We have reported the usefulness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the lymph node staging of lung cancer. EBUS-TBNA enables the sampling of histologic cores, which can be used for genetic analysis.

Methods: The purpose of this study was to develop and analyze the feasibility of detecting EGFR mutations in samples obtained by EBUS-TBNA. Forty-six patients with primary lung cancer in whom metastatic adenocarcinoma in the hilar and/or mediastinal lymph node was diagnosed by EBUS-TBNA were enrolled into the study. DNA was extracted from paraffin-embedded samples, and the EGFR mutation was analyzed in exons 19 and 21 using a newly developed loop-hybrid mobility shift assay. The results were confirmed by direct sequencing.

Results: Forty-three cases were eligible for analysis and in 11 cases, EGFR mutation (25.6%) was detected; one case was an in-frame deletion (E746-A750del) of exon 19, nine cases were point mutations (L858R) of exon 21, and one case was a double point mutation (L858R+L861V). All cases with EGFR mutations were confirmed by direct sequencing.

Conclusions: EGFR mutation can easily be detected in metastatic lymph nodes sampled by EBUS-TBNA. EBUS-TBNA allows genetic evaluations of tumor cells within the lymph node and may provide us with indications for EGFR-TKI therapy in the near future.

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