• Andreia Cristina de Melo, Vanessa Karen de Sá, Cinthya Sternberg, Eloisa Ribeiro Olivieri, Isabela Werneck da Cunha, Alexandre Todorovic Fabro, Dirce Maria Carraro, Milton José de Barros e Silva, Haynna Kimie Pimenta Inada, Evandro Sobrosa de Mello, Fernando Augusto Soares, Tereza Takagaki, Carlos Gil Ferreira, and Vera Luiza Capelozzi.
• Department of Pathology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
• Oncology. 2015 Jan 1;89(3):175-86.

AimTo 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.MethodsIn 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).ResultsEGFR 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.ConclusionsThese results indicate that the mutational profile and new IASLC/ATS/ERS classification provide additional prognostic information about lung ADC.© 2015 S. Karger AG, Basel.

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