title: The new histologic classification of lung primary adenocarcinoma subtypes is a reliable prognostic marker and identifies tumors with different mutation status: the experience of a French cohort.
abstract: BACKGROUND
  Histologic classification of lung adenocarcinoma subtype has a prognostic value in most studies. However, lung adenocarcinoma characteristics differ across countries. Here, we aimed at validating the prognostic value of this classification in a large French series of lung adenocarcinoma.
  
  
  METHODS
  We reviewed 407 consecutive lung adenocarcinomas operated on between 2001 and 2005 and reclassified them according to the International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification and subsequently graded them into low, intermediate, and high grade. We analyzed the relevance of this classification according to clinical, pathologic, and molecular analysis.
  
  
  RESULTS
  Patients (median age, 61 years; 288 men) underwent lobectomy (n = 378) or pneumonectomy (n = 29). Patients' overall survival at 5 and 10 years was 53.2% and 32.6%, respectively. Union for International Cancer Control stage distribution was 189 stage I, 104 stage II, 107 stage III, and seven stage IV. Low-grade tumor was found in one patient, intermediate grade in 275 patients, and high grade in 131 patients. KRAS and EGFR mutations were detected in 34% and 9.6%, respectively. Histologic grade was significantly correlated with extent of resection (P = .01), thyroid transcriptional factor-1 expression (P = .00000001), vascular emboli (P = .03), and EGFR mutations (P = .01). Mucinous adenocarcinomas were associated with KRAS mutations (P = .003). At univariate analysis, age, extent of resection, histologic grade, pleural invasion, vascular emboli, pathologic T and N, and stage were predictive of survival. At multivariate analysis, age (P = .0001), histologic grade (P = .03), and stage (P = .000003) were independent prognostic factors.
  
  
  CONCLUSIONS
  IASLC/ATS/ERS classification of lung adenocarcinomas predicts survival in French population. Histologic grade correlates with clinical, pathologic and molecular parameters suggesting different oncogenic pathways.
authors.affiliation: INSERM, U1138, Team Cancer, Immune Control, and Escape, Centre de Recherche des Cordeliers, Paris, France; Université Pierre et Marie Curie-Paris 6, Paris, France; Université Paris Descartes-Paris 5, Paris, France; Université Denis Diderot-Paris 7, Paris, France; Service de Pathologie, Paris, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Mansuet-Lupo
authors.affiliation: Hôpitaux Universitaire Paris Centre, AP-HP, Service de Chirurgie Thoracique, Paris, France.
authors.forename: Antonio
authors.initials: A
authors.lastname: Bobbio
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Paris, France; Université Paris Descartes-Paris 5, Paris, France; Hôpitaux Universitaire Paris Centre, AP-HP, Service de Chirurgie Thoracique, Paris, France; Hôpitaux Universitaire Paris Centre, AP-HP, Service de Biochimie, Paris, France; Hôpital Européen Georges Pompidou, AP-HP; and UMR-S775, Paris, France; INSERM, Faculté de médecine des Saints Pères, Paris, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Blons
authors.affiliation: INSERM, U1138, Team Cancer, Immune Control, and Escape, Centre de Recherche des Cordeliers, Paris, France; Université Pierre et Marie Curie-Paris 6, Paris, France; Université Paris Descartes-Paris 5, Paris, France; Université Denis Diderot-Paris 7, Paris, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Becht
authors.affiliation: INSERM, U1138, Team Cancer, Immune Control, and Escape, Centre de Recherche des Cordeliers, Paris, France.
authors.forename: Hanane
authors.initials: H
authors.lastname: Ouakrim
authors.affiliation: Hôpital Européen Georges Pompidou, AP-HP; and UMR-S775, Paris, France; INSERM, Faculté de médecine des Saints Pères, Paris, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Didelot
authors.affiliation: Service de Pathologie, Paris, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Charpentier
authors.affiliation: Service de Pathologie, Paris, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Bain
authors.affiliation: INSERM, U1138, Team Cancer, Immune Control, and Escape, Centre de Recherche des Cordeliers, Paris, France; Université Pierre et Marie Curie-Paris 6, Paris, France; Université Paris Descartes-Paris 5, Paris, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Marmey
authors.affiliation: INSERM, U1138, Team Cancer, Immune Control, and Escape, Centre de Recherche des Cordeliers, Paris, France; Université Pierre et Marie Curie-Paris 6, Paris, France; Université Paris Descartes-Paris 5, Paris, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Bonjour
authors.affiliation: INSERM, U1138, Team Cancer, Immune Control, and Escape, Centre de Recherche des Cordeliers, Paris, France; Université Pierre et Marie Curie-Paris 6, Paris, France; Université Paris Descartes-Paris 5, Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Biton
authors.affiliation: INSERM, U1138, Team Cancer, Immune Control, and Escape, Centre de Recherche des Cordeliers, Paris, France; Université Pierre et Marie Curie-Paris 6, Paris, France; Université Paris Descartes-Paris 5, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cremer
authors.affiliation: INSERM, U1138, Team Cancer, Immune Control, and Escape, Centre de Recherche des Cordeliers, Paris, France; Université Pierre et Marie Curie-Paris 6, Paris, France; Université Paris Descartes-Paris 5, Paris, France.
authors.forename: Marie-Caroline
authors.initials: MC
authors.lastname: Dieu-Nosjean
authors.affiliation: INSERM, U1138, Team Cancer, Immune Control, and Escape, Centre de Recherche des Cordeliers, Paris, France; Université Pierre et Marie Curie-Paris 6, Paris, France; Université Paris Descartes-Paris 5, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Sautès-Fridman
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Paris, France; Université Paris Descartes-Paris 5, Paris, France; Hôpitaux Universitaire Paris Centre, AP-HP, Service de Chirurgie Thoracique, Paris, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Régnard
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Paris, France; Université Paris Descartes-Paris 5, Paris, France; Hôpitaux Universitaire Paris Centre, AP-HP, Service de Chirurgie Thoracique, Paris, France; Hôpitaux Universitaire Paris Centre, AP-HP, Service de Biochimie, Paris, France; Hôpital Européen Georges Pompidou, AP-HP; and UMR-S775, Paris, France; INSERM, Faculté de médecine des Saints Pères, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Laurent-Puig
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Paris, France; Université Paris Descartes-Paris 5, Paris, France; Hôpitaux Universitaire Paris Centre, AP-HP, Service de Chirurgie Thoracique, Paris, France.
authors.forename: Marco
authors.initials: M
authors.lastname: Alifano
authors.affiliation: INSERM, U1138, Team Cancer, Immune Control, and Escape, Centre de Recherche des Cordeliers, Paris, France; Université Pierre et Marie Curie-Paris 6, Paris, France; Université Paris Descartes-Paris 5, Paris, France; Université Denis Diderot-Paris 7, Paris, France; Service de Pathologie, Paris, France. Electronic address: diane.damotte@htd.aphp.fr.
authors.forename: Diane
authors.initials: D
authors.lastname: Damotte
mesh_terms: D000230:Adenocarcinoma / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005602:France; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000145:classification* / Q000235:genetics* / Q000473:pathology; 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); D015203:Reproducibility of Results; D012189:Retrospective Studies; D015996:Survival Rate; 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