title: Validation of the IASLC/ATS/ERS lung adenocarcinoma classification for prognosis and association with EGFR and KRAS gene mutations: analysis of 440 Japanese patients.
abstract: BACKGROUND
  This study aimed to validate the utility of the new histological classification proposed by the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS) for identifying the prognostic subtypes of adenocarcinomas in Japanese patients; correlations between the classification and the presence of EGFR or KRAS mutation status were also investigated.
  
  
  METHODS
  We retrospectively reviewed 440 patients with lung adenocarcinoma, who underwent resection. The tumors were classified according to the IASLC/ATS/ERS classification. EGFR and KRAS mutations were detected using the established methods.
  
  
  RESULTS
  Five-year disease-free survival rates were: 100% for adenocarcinoma in situ (n = 20) and minimally invasive adenocarcinoma (n = 33), 93.8% for lepidic-predominant adenocarcinoma (n = 36), 88.8% for invasive mucinous adenocarcinoma (n = 10), 66.7% for papillary-predominant adenocarcinoma (n = 179), 69.7% for acinar-predominant adenocarcinoma (n = 61), 43.3% for solid-predominant adencoarcinoma (n = 78), and 0% for micropapillary-predominant adenocarcinoma (n = 19). Multivariate analysis revealed that the new classification was an independent predictor of disease-free survival. EGFR and KRAS mutations were detected in 90 cases (53.9%) and 21 cases (13.3%), respectively; EGFR mutations were significantly associated with adenocarcinoma in situ, minimally invasive adenocarcinoma, lepidic- and papillary-predominant adenocarcinoma, and KRAS mutations adenocarcinomas with mucinous tumor subtypes.
  
  
  CONCLUSIONS
  We found that the IASLC/ATS/ERS classification identified prognostic histologic subtypes of lung adenocarcinomas among Japanese patients. Histologic subtyping and molecular testing for EGFR and KRAS mutations can help predict patient prognosis and select those who require adjuvant chemotherapy.
authors.affiliation: Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan. akyoshi@shinshu-u.ac.jp
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshizawa
authors.forename: Shinji
authors.initials: S
authors.lastname: Sumiyoshi
authors.forename: Makoto
authors.initials: M
authors.lastname: Sonobe
authors.forename: Masashi
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Masakazu
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Fumi
authors.initials: F
authors.lastname: Kawakami
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Tsuruyama
authors.forename: William D
authors.initials: WD
authors.lastname: Travis
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Date
authors.forename: Hironori
authors.initials: H
authors.lastname: Haga
mesh_terms: D000230:Adenocarcinoma / Q000145:classification* / Q000235:genetics / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D007564:Japan; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000145:classification* / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009361:Neoplasm Invasiveness; D011013:Pneumonectomy; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins