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Original Research: CANCER |

Multigene Mutation Analysis of Metastatic Lymph Nodes in Non-small Cell Lung Cancer Diagnosed by Endobronchial Ultrasound-Guided Transbronchial Needle AspirationGene Mutation Analysis of Metastatic Lymph Nodes

Takahiro Nakajima, MD, PhD; Kazuhiro Yasufuku, MD, PhD, FCCP; Akira Nakagawara, MD, PhD; Hideki Kimura, MD, PhD; Ichiro Yoshino, MD, PhD
Author and Funding Information

From the Division of Thoracic Surgery (Drs Nakajima and Kimura), Chiba Cancer Center (Dr Nakagawara), Chiba, Japan; the Division of Thoracic Surgery (Drs Nakajima and Yasufuku), Toronto General Hospital, University Health Network, Toronto, ON, Canada; and the Department of General Thoracic Surgery (Drs Nakajima and Yoshino), Graduate School of Medicine, Chiba University, Chiba, Japan.

Correspondence to: Kazuhiro Yasufuku, MD, PhD, FCCP, Interventional Thoracic Surgery Program, University of Toronto, Division of Thoracic Surgery, Toronto General Hospital, University Health Network, 200 Elizabeth St, 9N-957, Toronto, ON, M5G2C4, Canada; e-mail: Kazuhiro.Yasufuku@uhn.on.ca


Part of this article has been published in abstract form (Nakajima T, Yasufuku K, Nakagawara A, et al. Chest. 2010;138(4)(suppl 4):728A).

Funding/Support: This research was supported in part by the Ministry of Education, Culture, Sports, Science, and Technology, Grant-in-Aid for Young Scientists (B) [Grant 21791340 in 2009] (T. N.), and Grant-in-Aid for Cancer Research from Ministry of Health, Labor and Welfare in 2009 (T. N.).

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2011 American College of Chest Physicians


Chest. 2011;140(5):1319-1324. doi:10.1378/chest.10-3186
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Background:  The importance of biomarker analysis in patients with non-small cell lung cancer (NSCLC) is well known. The purpose of this study was to analyze the mutation status of multiple genes in metastatic lymph nodes obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and to examine the correlation between treatments and outcomes.

Methods:  Genetic alterations were analyzed in metastatic hilar or mediastinal lymph nodes diagnosed by EBUS-TBNA in 156 patients with NSCLC. Epidermal growth factor receptor (EGFR) was analyzed using the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method (n = 156). V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-ras) (exons 2-3) and tumor protein 53 (p53) (exons 4-8) were analyzed by direct sequencing (n = 113). In addition, retrospective chart review was performed for clinical data analysis.

Results:  EGFR gene mutations were detected in 42 cases (26.9%). Twenty-three patients with EGFR mutations received gefitinib, with an overall response rate (partial response [PR]) of 54.5% and disease control rate (PR + stable disease) of 86.4% (Response Evaluation Criteria in Solid Tumors). K-ras gene mutations were detected in four cases (3.5%), and p53 gene mutations were detected in 47 cases (41.6%). Fifty-two patients underwent conventional chemotherapy (46 patients underwent platinum-based chemotherapy). Patients with p53 gene mutations showed chemoresistance (progressive disease of 42.9%, P = .0339) and a relatively poor prognosis after chemotherapy (P = .1391).

Conclusions:  Multigene mutation analysis can be performed in EBUS-TBNA samples of metastatic lymph nodes from patients with NSCLC. EBUS-TBNA allows genetic evaluation of tumor cells within the metastatic node, which may allow physicians to better select treatments, particularly EGFR tyrosine kinase inhibitors.


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