Bronchoscopic microsampling is a useful complementary diagnostic tool for detecting lung cancer.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Yasuda
Hiroyuki
H
Department of Pulmonary Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Soejima
Kenzo
K
Nakayama
Sohei
S
Kawada
Ichiro
I
Nakachi
Ichiro
I
Yoda
Satoshi
S
Satomi
Ryosuke
R
Ikemura
Shinnosuke
S
Terai
Hideki
H
Sato
Takashi
T
Watanabe
Hideo
H
Naoki
Katsuhiko
K
Hayashi
Yuichiro
Y
Ishizaka
Akitoshi
A
D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D001706:Biopsy; D001992:Bronchoalveolar Lavage Fluid; D001999:Bronchoscopy; D018797:Cell Cycle Proteins / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D050939:Gene Fusion; D006801:Humans; D008168:Lung / Q000473:pathology*; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D012680:Sensitivity and Specificity; D012697:Serine Endopeptidases / Q000235:genetics
D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; C415585:EML4 protein, human; D012697:Serine Endopeptidases