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

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

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)32-38
Number of pages7
JournalLung Cancer
Volume72
Issue number1
DOIs
Publication statusPublished - 2011 Apr

Fingerprint

Lung Neoplasms
Tumor Suppressor Genes
Serum
Epigenomics
Mutation
DNA
Lung
Gene Rearrangement
Gene Fusion
DNA Methylation
Early Detection of Cancer
Nucleic Acids
Methylation
Early Diagnosis
Neoplasms
Phosphotransferases
Polymerase Chain Reaction

Keywords

  • Bronchoscopic microsampling
  • EGFR mutation
  • EML4-ALK
  • Epigenetics
  • Epithelial lining fluid
  • Lung cancer

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

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.

In: Lung Cancer, Vol. 72, No. 1, 04.2011, p. 32-38.

Research output: Contribution to journalArticle

Yasuda, H, Soejima, K, Nakayama, S, Kawada, I, Nakachi, I, Yoda, S, Satomi, R, Ikemura, S, Terai, H, Sato, T, Watanabe, H, Naoki, K, Hayashi, Y & Ishizaka, A 2011, 'Bronchoscopic Microsampling is a Useful Complementary Diagnostic Tool for Detecting Lung Cancer', Lung Cancer, vol. 72, no. 1, pp. 32-38. https://doi.org/10.1016/j.lungcan.2010.07.016
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. / Bronchoscopic Microsampling is a Useful Complementary Diagnostic Tool for Detecting Lung Cancer. In: Lung Cancer. 2011 ; Vol. 72, No. 1. pp. 32-38.
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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.",
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AU - Yoda, Satoshi

AU - Satomi, Ryosuke

AU - Ikemura, Shinnosuke

AU - Terai, Hideki

AU - Sato, Takashi

AU - Watanabe, Hideo

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AU - Hayashi, Yuichiro

AU - Ishizaka, Akitoshi

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N2 - 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.

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