title: Epidermal growth factor receptor mutations in adenocarcinoma in situ and minimally invasive adenocarcinoma detected using mutation-specific monoclonal antibodies.
abstract: Epidermal growth factor receptor (EGFR) mutation rates in adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) were studied using both DNA analysis and mutation-specific immunohistochemistry.
  
  
  
  The peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method was used to detect mutations in exons 18, 19, 20, and 21 of the EGFR gene in DNA samples extracted from paraffin-embedded tissue sections. Simultaneously, immunohistochemical analysis with two EGFR mutation-specific monoclonal antibodies was used to identify proteins resulting from an in-frame deletion in exon 19 (E746_A750del) and a point mutation replacing leucine with arginine at codon 858 of exon 21 (L858R).
  
  
  
  Forty-three tumors (22 AIS and 21 MIA) were examined. The EGFR mutation rate in AIS detected by DNA analysis was 27.3% (L858R, 5/22; exon 19 deletion,1/22), whereas that detected in MIA was 42.9% (L858R,4/21; exon 19 deletion,5/21). Mutations detected by immunohistochemical analysis included 22.7% (L858R, 4/22; exon 19 deletion, 1/22) in AIS and 42.9% (L858R, 4/21; exon 19 deletion, 5/21) in MIA. Although some results were contradictory, concordant results were obtained using both assays in 38 of 43 cases (88.4%).
  
  
  
  DNA and immunohistochemical analyses revealed similar EGFR mutation rates in both MIA and AIS, suggesting that mutation-specific monoclonal antibodies are useful to confirm DNA assay results.
authors: Department of Chest Surgery, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan. Electronic address: h-nakamura@marianna-u.ac.jp.
authors: Haruhiko
authors: H
authors: Nakamura
authors: Department of Pathology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
authors: Hirotaka
authors: H
authors: Koizumi
authors: Department of Chest Surgery, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
authors: Hiroyuki
authors: H
authors: Kimura
authors: Department of Chest Surgery, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
authors: Hideki
authors: H
authors: Marushima
authors: Department of Chest Surgery, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
authors: Hisashi
authors: H
authors: Saji
authors: Department of Pathology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
authors: Masayuki
authors: M
authors: Takagi
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D065311:Adenocarcinoma in Situ / Q000235:genetics* / Q000473:pathology*; D000368:Aged; D000911:Antibodies, Monoclonal; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging
chemical_list: D000911:Antibodies, Monoclonal; D066246:ErbB Receptors
keywords: Early adenocarcinoma; Epidermal growth factor receptor mutation; Immunohistochemistry; Lung cancer; Subtype