Bronchoscopic Microsampling is a Useful Complementary Diagnostic Tool for Detecting Lung Cancer

Yasuda, Hiroyuki; Soejima, Kenzo; Nakayama, Sohei; Kawada, Ichiro; Nakachi, Ichiro; Yoda, Satoshi; Satomi, Ryosuke; Ikemura, Shinnosuke; Terai, Hideki; Sato, Takashi; Watanabe, Hideo; Naoki, Katsuhiko; Hayashi, Yuichiro; Ishizaka, Akitoshi

doi:10.1016/j.lungcan.2010.07.016

« Previous Next »Lung Cancer
Volume 72, Issue 1 , Pages 32-38, April 2011

Bronchoscopic Microsampling is a Useful Complementary Diagnostic Tool for Detecting Lung Cancer

Hiroyuki Yasuda
- Department of Pulmonary Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
- These authors contributed equally to this work
Kenzo Soejima
- Department of Pulmonary Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
- Corresponding author. Department of Pulmonary Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Tel.: +81 3 3353 1211x61430; fax: +81 3 3353 2502.
Sohei Nakayama
- Department of Pulmonary Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
- These authors contributed equally to this work
Ichiro Kawada
- Department of Pulmonary Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Ichiro Nakachi
- Department of Pulmonary Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Satoshi Yoda
- Department of Pulmonary Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Ryosuke Satomi
- Department of Pulmonary Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Shinnosuke Ikemura
- Department of Pulmonary Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Hideki Terai
- Department of Pulmonary Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Takashi Sato
- Department of Pulmonary Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Hideo Watanabe
- Department of Pulmonary Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Katsuhiko Naoki
- Department of Pulmonary Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Yuichiro Hayashi
- Department of Pathology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Akitoshi Ishizaka
- Department of Pulmonary Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan

Received 17 May 2010; received in revised form 24 July 2010; accepted 30 July 2010. published online 03 September 2010.

Abstract

Purpose

Bronchoscopic microsampling (BMS) is a novel and direct method with which to obtain epithelial lining fluid (ELF) from the lungs. Analysis of DNA hypermethylation of tumor suppressor genes (TSGs) is expected to be a sensitive tool for the early detection of lung cancer. It has been reported that the existence of EGFR mutations and EML4-ALK gene rearrangements are related to the sensitivity of corresponding kinase inhibitors. We aimed to evaluate the suitability of ELF as a sample for analyzing molecular changes specific for lung cancer.

Patients and methods

We collected ELF from 61 lung cancer patients by BMS from the airway close to the peripheral lung nodule and purified the nucleic acids. We performed methylation specific PCR in each ELF as well as matched serum and tumor tissue for TSGs for DNA methylation analysis. We also examined EGFR mutations and EML4-ALK rearrangement.

Results

The sensitivity for detecting DNA hypermethylation in ELF vs serum was 74.1% vs 18.5%. We found 60.1% of patients had at least one hypermethylation in ELF, while only 27.9% had it in serum. Of note, DNA hypermethylation was detected even in stage I patients (60.0%) and the detection rate was almost the same level in each stage. We also found the sensitivity for detecting EGFR mutation in ELF vs serum was 58.3% vs 8.3%. We detected an EML4-ALK fusion gene using ELF in one patient.

Conclusions

BMS is an alternative method to detect cancer specific genetic and epigenetic alterations and will be a useful complementary diagnostic tool for lung cancer.

Summary

Investigation of genetic and epigenetic changes associated with lung cancer has clinical importance for its diagnosis and management. The clinical usefulness of bronchoscopic microsampling (BMS) in lung cancer has not yet been evaluated. This study demonstrates that BMS could be useful for detecting lung cancer specific molecular changes and valuable for early diagnosis and determination of treatment options for lung cancer.

Keywords: bronchoscopic microsampling, lung cancer, epigenetics, epithelial lining fluid, EGFR mutation, EML4-ALK