Mutational Profile and New IASLC/ATS/ERS Classification Provide Additional Prognostic Information about Lung Adenocarcinoma: A Study of 125 Patients from Brazil

Abstract

Aim: 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.

Prevalence of EGFR Mutations in Lung Cancer in Uruguayan Population

“…This supports the genetic heterogeneity of NSCLC among geographic regions and also underscores the need for extending the study to other countries of South and Central America. Several studies conducted in Brazil reported 24% of EGFR mutation in adenocarcinomas [30], in agreement with De Melo et al, who reported 21.6% [37]. Interestingly, in this study most are rare mutations, while common mutations in exon 19 and 21 represent only 40% of the total mutations.…”

Primary adenocarcinoma of the lung – histological subtypes and outcome after surgery, using the IASLC/ATS/ERS classification of lung adenocarcinoma

“…The mean size of the tumors was 2.8 AE 2.1 cm (range; 0. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19].…”

“…Non‐small cell lung carcinoma (NSCLC) accounts for 85% of all lung cancer where adenocarcinoma (AC) is the most common histology . The strongest prognostic factors of survival for patients with NSCLC are the TNM stage , advanced age, history of weight loss , ethnicity , and some genetic mutations (i.e., EGFR, K‐RAS, p53) .The three major NSCLC histological types; squamous cell carcinoma (SCC), AC, and large cell carcinoma (LCC) have also been shown to influence survival in some studies , but not in all . Bronchioloalveolar adenocarcinoma (BAC) that was described as a subtype of AC, has been thought to have a better prognosis than non‐BAC adenocarcinomas .…”

Padrões de tratamento, uso de recursos e custo do câncer de pulmão de não pequenas células avançado em instituições brasileiras privadas

“…Entre os pacientes testados, 35,3% eram positivos para EGFR, dado similar ao percentual relatado em Bacchi et al, que identificaram 30,4% de EGFR positivo entre todas as amostras testadas (Bacchi et al, 2012). Por outro lado, a maioria dos estudos publicados sobre o status de mutação do EGFR reporta um percentual menor de pacientes positivos no Brasil, América Latina, Austrália, Estados Unidos e Europa (de Castro et al, 2017;Pan et al, 2013;de Marinis et al, 2014;Gridelli et al, 2014;Honma et al, 2014;Carneiro et al, 2014;de Melo et al, 2015;Arrieta et al, 2015), exceto Coreia do Sul e Taiwan (de Castro et al, 2017). Em relação à mutação do KRAS, a taxa de pacientes positivos é maior em comparação com a literatura (Bacchi et al, 2012;Carneiro et al, 2014;de Melo et al, 2015;Arrieta et al, 2015), provavelmente devido ao número reduzido de pacientes testados neste estudo (n = 9 Melo et al, 2015), mas menor que na Coreia do Sul e em Taiwan (de Castro et al, 2017).…”

“…Por outro lado, a maioria dos estudos publicados sobre o status de mutação do EGFR reporta um percentual menor de pacientes positivos no Brasil, América Latina, Austrália, Estados Unidos e Europa (de Castro et al, 2017;Pan et al, 2013;de Marinis et al, 2014;Gridelli et al, 2014;Honma et al, 2014;Carneiro et al, 2014;de Melo et al, 2015;Arrieta et al, 2015), exceto Coreia do Sul e Taiwan (de Castro et al, 2017). Em relação à mutação do KRAS, a taxa de pacientes positivos é maior em comparação com a literatura (Bacchi et al, 2012;Carneiro et al, 2014;de Melo et al, 2015;Arrieta et al, 2015), provavelmente devido ao número reduzido de pacientes testados neste estudo (n = 9 Melo et al, 2015), mas menor que na Coreia do Sul e em Taiwan (de Castro et al, 2017). Os regimes baseados em platina foram a prática clínica mais comum como terapia de primeira linha (83,6%), conforme recomendado pelas diretrizes nacionais e internacionais (NCCN, 2017;de Sa et al, 2016) e também foram o tratamento predominante nos estudos de dados do mundo real publicados na Ásia-Pacífico, América do Norte e Europa (de Castro et al, 2017;Davis et al, 2015;Sacher et al, 2015;Solem et al, 2015a;Davies et al, 2017).…”