title: Epithelial-mesenchymal transition in EGFR-TKI acquired resistant lung adenocarcinoma.
abstract: BACKGROUND
  The epithelial to mesenchymal transition (EMT) may well play a part in determining the sensitivity to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). However to date, no study has investigated the association between the EMT status and acquired resistance using cancer specimens.
  
  
  METHODS
  Immunohistochemical (IHC) staining was used to analyse the protein expression of epithelial and mesenchymal markers in tumour samples from lung adenocarcinoma patients. Mutations in the EGFR and K-ras gene were also examined.
  
  
  RESULTS
  All patients showed a positive expression of epithelial markers in sensitive tumours. Tumour in 4 (44.4%) out of 9 patients showed down-regulation of epithelial markers or up-regulation of mesenchymal markers. The change in the EMT status between pre-and post-treatment was shown in 2 cases each with and without the T790M mutation.
  
  
  CONCLUSIONS
  EMT plays a role in approximately half of the cases of resistance to EGFR-TKI, independent of T790M mutation.
authors.affiliation: Second Department of Surgery, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan. hidetaka@med.uoeh-u.ac.jp
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Uramoto
authors.forename: Teruo
authors.initials: T
authors.lastname: Iwata
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Onitsuka
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Shimokawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hanagiri
authors.forename: Tsunehiro
authors.initials: T
authors.lastname: Oyama
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D000368:Aged; D000369:Aged, 80 and over; D019008:Drug Resistance, Neoplasm; D004847:Epithelial Cells / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005260:Female; D000077156:Gefitinib; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D008297:Male; D008648:Mesoderm / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D011799:Quinazolines / Q000494:pharmacology; D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D011799:Quinazolines; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000077156:Gefitinib