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Original Research: Lung Cancer |

The New Histologic Classification of Lung Primary Adenocarcinoma Subtypes Is a Reliable Prognostic Marker and Identifies Tumors With Different Mutation StatusPrognostic Factors in Lung Adenocarcinoma: The Experience of a French Cohort

Audrey Mansuet-Lupo, MD; Antonio Bobbio, MD, PhD; Hélène Blons, PharmD, PhD; Etienne Becht; Hanane Ouakrim; Audrey Didelot; Marie-Christine Charpentier, MD; Serge Bain; Béatrice Marmey; Patricia Bonjour; Jérôme Biton, PhD; Isabelle Cremer, PhD; Marie-Caroline Dieu-Nosjean, PhD; Catherine Sautès-Fridman, PhD; Jean-François Régnard, MD; Pierre Laurent-Puig, MD, PhD; Marco Alifano, MD, PhD, FCCP; Diane Damotte, MD, PhD
Author and Funding Information

From INSERM (Drs Mansuet-Lupo, Biton, Cremer, Dieu-Nosjean, Sautès-Fridman, and Damotte, Mr Becht, and Mss Ouakrim, Marmey, and Bonjour) U1138, Team Cancer, Immune Control, and Escape, Centre de Recherche des Cordeliers; the Université Pierre et Marie Curie-Paris 6 (Drs Mansuet-Lupo, Biton, Cremer, Dieu-Nosjean, Sautès-Fridman and Damotte, Mr Becht, and Mss Marmey and Bonjour); the Université Paris Descartes-Paris 5 (Drs Mansuet-Lupo, Blons, Biton, Cremer, Dieu-Nosjean, Sautès-Fridman, Régnard, Laurent-Puig, Alifano, and Damotte, Mr Becht, and Mss Marmey and Bonjour); the Université Denis Diderot-Paris 7 (Drs Mansuet-Lupo and Damotte and Mr Becht); Service de Pathologie (Drs Mansuet-Lupo and Damotte, Ms Charpentier, and Mr Bain), Hôpitaux Universitaire Paris Centre, AP-HP; the Service de Chirurgie Thoracique (Drs Bobbio, Régnard, and Alifano), Hôpitaux Universitaire Paris Centre, AP-HP; the Service de Biochimie (Drs Blons and Laurent-Puig), Hôpital Européen Georges Pompidou, AP-HP; and UMR-S775 (Drs Blons and Laurent-Puig and Ms Didelot), INSERM, Faculté de médecine des Saints Pères, Paris, France.

CORRESPONDENCE TO: Diane Damotte, MD, PhD, Service de Pathologie, Hôpitaux Universitaire Paris Centre, 1, Place du Parvis de Notre Dame, 75181, Paris, France; e-mail: diane.damotte@htd.aphp.fr


Drs Mansuet-Lupo and Bobbio contributed equally to this work.

FUNDING/SUPPORT: This work was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Descartes, Université Pierre et Marie Curie, Institut National du Cancer and Cancéropole Ile de France [Grants 2011-1-PLBIO-06-INSERM 6-1, 2009-1-PLBIO-07-INSERM 6-1, 2010-1-PLBIO-03-INSERM 6-1, 11LAXE62_9UMRS872 FRIDMAN] and Fondation ARC pour la Recherche sur le Cancer [Grant SL220110603483].

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;146(3):633-643. doi:10.1378/chest.13-2499
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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.

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