title: Correlation of mutation status and survival with predominant histologic subtype according to the new IASLC/ATS/ERS lung adenocarcinoma classification in stage III (N2) patients.
abstract: BACKGROUND
  We investigated the relationship between predominant subtype, according to the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Lung Adenocarcinoma Classification; mutation status; and patient outcome in stage III (N2) lung adenocarcinoma.
  
  
  METHODS
  We identified 69 patients with stage III (N2) lung adenocarcinoma operated on with curative intent between 1993 and 2011 who had adequate tumor tissue for molecular analysis and adequate follow-up time for survival analysis. DNA was isolated and tested for mutations using Sequenom's OncoCarta Panel (v1.0; Sequenom, San Diego, CA).
  
  
  RESULTS
  The majority of tumors were acinar (26 of 69 tumors; 38%), solid (24 of 69 tumors; 35%), and micropapillary predominant (13 of 69 tumors; 19%) subtypes. EGFR and KRAS mutations were identified in 17 of 59 tumors (29%) and 13 of 59 tumors (22%), respectively. EGFR mutations occurred most often in acinar (11 of 25 tumors; 44%) and micropapillary predominant tumors (five of 13 tumors; 38%) (p = 0.009), whereas KRAS mutations occurred most often in solid predominant tumors (nine of 21 tumors; 43%) (p = 0.016). Patients with acinar predominant tumors had significantly improved overall survival compared with those with non-acinar predominant tumors (hazard ratio: 0.45; 95% confidence interval: 0.22-0.91; p = 0.026), which remained significant after adjustment for EGFR status, T-stage, sex, and age. Patients with EGFR-mutant micropapillary predominant tumors had similar survival to those with EGFR-mutant acinar predominant tumors. The predominant subtype in the primary tumor was most often seen in the N2 node in micropapillary and solid predominant tumors but not in acinar predominant tumors.
  
  
  CONCLUSIONS
  The predominant subtype in the primary tumor was associated with overall survival in resected stage III (N2) lung adenocarcinoma and was independent of mutation status. Histologic subtyping provides important prognostic information and potentially molecular correlates.
authors.affiliation: Department of Anatomical Pathology, St Vincent's Hospital, The University of Melbourne, Melbourne, Australia. prue.russell@svhm.org.au
authors.forename: Prudence A
authors.initials: PA
authors.lastname: Russell
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Barnett
authors.forename: Marzena
authors.initials: M
authors.lastname: Walkiewicz
authors.forename: Zoe
authors.initials: Z
authors.lastname: Wainer
authors.forename: Matthew
authors.initials: M
authors.lastname: Conron
authors.forename: Gavin M
authors.initials: GM
authors.lastname: Wright
authors.forename: Julian
authors.initials: J
authors.lastname: Gooi
authors.forename: Simon
authors.initials: S
authors.lastname: Knight
authors.forename: Rochelle
authors.initials: R
authors.lastname: Wynne
authors.forename: Danny
authors.initials: D
authors.lastname: Liew
authors.forename: Thomas
authors.initials: T
authors.lastname: John
mesh_terms: D000230:Adenocarcinoma / Q000145:classification / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002291:Carcinoma, Papillary / Q000235:genetics / Q000401:mortality / Q000556:secondary*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000145:classification / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D015996:Survival Rate; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins