title: Mutational Profile and New IASLC/ATS/ERS Classification Provide Additional Prognostic Information about Lung Adenocarcinoma: A Study of 125 Patients from Brazil.
abstract: OBJECTIVE
  To show additional prognostic information about the mutational profile and new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification of adenocarcinoma (ADC) in patients without epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor treatments.
  
  
  METHODS
  In human lung ADC patients (n = 125), including 24 lepidic, 67 acinar, 23 papillary, and 11 solid predominant subtypes, EGFR and KRAS were sequenced, and anaplastic lymphoma kinase (ALK) rearrangements were screened using fluorescence in situ hybridization (FISH).
  
  
  RESULTS
  EGFR was mutated in 21.6% of patients with 19.57% showing a mean expression. The most frequent EGFR mutation was a deletion in exon 19, followed by an L858R amino acid substitution in exon 21. KRAS was mutated in 26.4% of patients with 50% displaying mean expression. ALK rearrangement was detected in 6 patients (4.8%). Predominant acinar ADC was strongly associated with EGFR and KRAS mutation. Clinical stage, lymph node metastases, and EGFR mutation in exon 18 showed a significant difference in disease-free and overall survival, but only a trend significance for EGFR and KRAS mutations. Multivariate analysis revealed that men aged >71 years, with a history of smoking (<72 packs/year), clinical stage I/II, and acinar histologic subtype presented better survival than women aged ≤ 71 years, with a history of smoking (>72 packs/year), and having a predominant solid ADC and EGFR mutation in exon 18.
  
  
  CONCLUSIONS
  These results indicate that the mutational profile and new IASLC/ATS/ERS classification provide additional prognostic information about lung ADC.
authors.affiliation: Department of Pathology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Andreia Cristina
authors.initials: AC
authors.lastname: de Melo
authors.forename: Vanessa
authors.initials: V
authors.lastname: Karen de Sá
authors.forename: Cinthya
authors.initials: C
authors.lastname: Sternberg
authors.forename: Eloisa Ribeiro
authors.initials: ER
authors.lastname: Olivieri
authors.forename: Isabela
authors.initials: I
authors.lastname: Werneck da Cunha
authors.forename: Alexandre Todorovic
authors.initials: AT
authors.lastname: Fabro
authors.forename: Dirce Maria
authors.initials: DM
authors.lastname: Carraro
authors.forename: Milton José
authors.initials: MJ
authors.lastname: de Barros e Silva
authors.forename: Haynna Kimie
authors.initials: HK
authors.lastname: Pimenta Inada
authors.forename: Evandro Sobrosa
authors.initials: ES
authors.lastname: de Mello
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
authors.forename: Tereza
authors.initials: T
authors.lastname: Takagaki
authors.forename: Carlos Gil
authors.initials: CG
authors.lastname: Ferreira
authors.forename: Vera Luiza
authors.initials: VL
authors.lastname: Capelozzi
mesh_terms: D000230:Adenocarcinoma / Q000145:classification* / Q000209:etiology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000231:Adenocarcinoma, Papillary / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D000077548:Anaplastic Lymphoma Kinase; D001938:Brazil; D018267:Carcinoma, Acinar Cell / Q000235:genetics; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D006801:Humans; D008175:Lung Neoplasms / Q000145:classification* / Q000209:etiology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D059645:Mutation Rate; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D016019:Survival Analysis; D059467:Transcriptome; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins