title: MassARRAY, pyrosequencing, and PNA clamping for EGFR mutation detection in lung cancer tissue and cytological samples: a multicenter study.
abstract: BACKGROUND
  Testing for epidermal growth factor receptor (EGFR) mutation is an important process in the therapeutic plan of patients with lung cancer. Recently, MassARRAY, based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, has been shown to be a useful method for somatic mutation analysis with pyrosequencing and peptide nucleic acid clamping (PNAc).
  
  
  METHODS
  A total of 107 tissues and 67 cytological samples, which were confirmed to have lung adenocarcinoma at nine hospitals in Korea, were collected. Among the MassARRAY, pyrosequencing, and PNAc, the concordance rates and sensitivity of EGFR mutation detection were analyzed and validated in comparative tissue and cytological specimens.
  
  
  RESULTS
  The concordance rate between pyrosequencing and PNAc was higher than that between MassARRAY and either of the pyrosequencing and PNAc in both tissue and cytological samples. In a comparison of diagnostic performance, MassARRAY (sensitivity: 85.7 %) was higher than pyrosequencing (74.3 %) and PNAc (70 %) in tissue, although pyrosequencing (80.5 %) was more highly sensitive, compared to MassARRAY (70.7 %) and PNAc (70.7 %) in terms of cytology. Unexpectedly, use of MassARRAY resulted in a significantly different EGFR mutation detection rate between tissue and cytological samples.
  
  
  CONCLUSIONS
  When used for the detection of EGFR mutations, MassARRAY was more sensitive than pyrosequencing or PNA clamping in tissue, but not in cytological samples. In EGFR mutation detection between tissues and cytology, PNAc showed relatively higher concordance than MassARRAY or pyrosequencing.
authors.affiliation: Department of Pathology, Hanyang University Guri Hospital, Hanyang University College of Medicine, 153, Gyeongchun-ro, Guri-si, Gyeonggi-do, 11923, South Korea.
authors.forename: Kyueng-Whan
authors.initials: KW
authors.lastname: Min
authors.affiliation: Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, 120-1, Neungdong-ro, Gwangjin-gu, Seoul, 05030, South Korea. wskim@kuh.ac.kr.
authors.forename: Wan-Seop
authors.initials: WS
authors.lastname: Kim
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olymphic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Jang
authors.affiliation: Department of Pathology, Chonnam National University Hospital, Chonnam National University Medical School, 160, Baekseo-ro, Dong-gu, Gwangju, 61469, South Korea.
authors.forename: Yoo Duk
authors.initials: YD
authors.lastname: Choi
authors.affiliation: Department of Pathology, Inje Unversity Ilsan Paik Hospital, Inje University School of Medicine, 170, Juhwa-ro, Ilsanseo-gu, Goyang-si, Gyeonggi-do, 10380, South Korea.
authors.forename: Sunhee
authors.initials: S
authors.lastname: Chang
authors.affiliation: Department of Pathology, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, 20, Ilsan-ro, Wonju-si, Gangwon-do, 26426, South Korea.
authors.forename: Soon Hee
authors.initials: SH
authors.lastname: Jung
authors.affiliation: Department of Pathology, Inha University Hospital, Inha University School of Medicine, 27, Inhang-ro, Jung-gu, Incheon, 22332, South Korea.
authors.forename: Lucia
authors.initials: L
authors.lastname: Kim
authors.affiliation: Department of Pathology, Dong-A University Hospital, Dong-A University College of Medicine, 26, Daesingongwon-ro, Seo-gu, Busan, 49201, South Korea.
authors.forename: Mee-Sook
authors.initials: MS
authors.lastname: Roh
authors.affiliation: Department of Pathology, Chungnam National University Hospital, Chungnam National University College of Medicine, 282, Munhwa-ro, Jung-gu, Daejeon, 35015, South Korea.
authors.forename: Choong Sik
authors.initials: CS
authors.lastname: Lee
authors.affiliation: Department of Pathology, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, 7, Keunjaebong-gil, Hwaseong-si, Gyeonggi-do, 18450, South Korea.
authors.forename: Jung Weon
authors.initials: JW
authors.lastname: Shim
authors.affiliation: Department of Pathology, Yeungnam University Medical Center, Yeungnam University College of Medicine, 170, Hyeonchung-ro, Nam-gu, Daegu, 42415, South Korea.
authors.forename: Mi Jin
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Department of Pathology, National Cancer Center, 323, Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10408, South Korea.
authors.forename: Geon Kook
authors.initials: GK
authors.lastname: Lee
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D004252:DNA Mutational Analysis / Q000379:methods; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005557:Formaldehyde; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation; D016612:Paraffin Embedding; D020135:Peptide Nucleic Acids / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D016707:Tissue Fixation
chemical_list: D020135:Peptide Nucleic Acids; D005557:Formaldehyde; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR mutation; Lung adenocarcinoma; Mass spectrometry, pyrosequencing; Peptide nucleic acid