title: Multiplexed molecular profiling of lung cancer using pleural effusion.
abstract: BACKGROUND
  Pleural effusion is frequently observed in patients with advanced lung cancer. Although effusion can be obtained less invasively and repeatedly, its use in multiplexed molecular profiling has not been fully investigated.
  
  
  METHODS
  Between July 2011 and April 2013, pleural effusion samples were obtained from patients with lung cancer at Shizuoka Cancer Center. They were analyzed for EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN, and HER2 mutations, EGFR, MET, FGFR1, FGFR2, and PIK3CA amplifications, and ALK, ROS1, and RET fusion genes using pyrosequensing and/or capillary electrophoresis, quantitative reverse-transcriptase polymerase chain reaction, and reverse-transcriptase polymerase chain reaction, respectively.
  
  
  RESULTS
  One hundred and two samples from 84 patients were analyzed. Adenocarcinoma was the most common histological subtype (82%). Genetic abnormalities were detected in 42% of patients. The most common abnormality was EGFR mutation (29%), followed by EML4-ALK rearrangement (5%), KRAS mutation, and EGFR amplification (4%, each). Concordance rates between pleural effusion and matched formalin-fixed, paraffin-embedded samples were 88%. Among 11 patients who provided samples at multiple time points, changes in molecular profile over the course of treatment were observed in five patients.
  
  
  CONCLUSIONS
  The use of pleural effusion for multiplexed molecular testing and real-time monitoring in lung cancer was demonstrated.
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Shimonagakubo; Division of Drug Discovery and Development, Shizuoka Cancer Center Research Institute, Nagaizumi-cho, Sunto-gun, Shizuoka; Third Department of Internal Medicine, Wakayama Medical University, Kimiidera, Wakayama.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Akamatsu
authors.affiliation: Division of Drug Discovery and Development, Shizuoka Cancer Center Research Institute, Nagaizumi-cho, Sunto-gun, Shizuoka. Electronic address: ykoh@wakayama-med.ac.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Koh
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Shimonagakubo.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Kenmotsu
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Shimonagakubo.
authors.forename: Tateaki
authors.initials: T
authors.lastname: Naito
authors.affiliation: Division of Drug Discovery and Development, Shizuoka Cancer Center Research Institute, Nagaizumi-cho, Sunto-gun, Shizuoka.
authors.forename: Masakuni
authors.initials: M
authors.lastname: Serizawa
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Shimonagakubo; Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka.
authors.forename: Madoka
authors.initials: M
authors.lastname: Kimura
authors.affiliation: Clinical Trial Management Department, Shizuoka Cancer Center, Shimonagakubo, Nagaizumi-cho Sunto-gun, Shizuoka.
authors.forename: Keita
authors.initials: K
authors.lastname: Mori
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Shimonagakubo.
authors.forename: Hisao
authors.initials: H
authors.lastname: Imai
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Shimonagakubo.
authors.forename: Akira
authors.initials: A
authors.lastname: Ono
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Shimonagakubo; Department of Respiratory Medicine, Juntendo University, Tokyo.
authors.forename: Takehito
authors.initials: T
authors.lastname: Shukuya
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Shimonagakubo.
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Taira
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Shimonagakubo.
authors.forename: Haruyasu
authors.initials: H
authors.lastname: Murakami
authors.affiliation: Division of Thoracic Surgery, Nagaizumi-cho Sunto-gun, Shizuoka, Japan.
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Ohde
authors.affiliation: Division of Diagnostic Radiology, Nagaizumi-cho Sunto-gun, Shizuoka, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Endo
authors.affiliation: Division of Diagnostic Pathology, Shizuoka Cancer Center, Shimonagakubo, Nagaizumi-cho Sunto-gun, Shizuoka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakajima
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Shimonagakubo.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Shimonagakubo; Third Department of Internal Medicine, Wakayama Medical University, Kimiidera, Wakayama.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamamoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058534:Class I Phosphatidylinositol 3-Kinases; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D005784:Gene Amplification; D020869:Gene Expression Profiling; D050939:Gene Fusion; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D048369:MAP Kinase Kinase 1 / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D010996:Pleural Effusion / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*
chemical_list: C522504:EML4-ALK fusion protein, human; D008565:Membrane Proteins; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D020794:Receptor Protein-Tyrosine Kinases; D048369:MAP Kinase Kinase 1; D051059:PTEN Phosphohydrolase; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human