SESSION TYPE: Biomarkers, Oncogenes and Enhanced Bronchoscopy in NSCLC
PRESENTED ON: Wednesday, October 24, 2012 at 02:45 PM - 04:15 PM
PURPOSE: We performed this analysis to reveal the association between 5 well-identified oncogenic driver mutations with clinical and pathological features in lung adenocarcinomas from smokers. This document may have the potential to optimize existing treatment strategies and clinical trial design.
METHODS: In this series, 230 resected lung adenocarcinoma from smokers (>100 cigarettes in a life time) at a single institution (Fudan University, Shanghai, China) were analyzed for mutation in EGFR, KRAS, BRAF, HER2 and EML4-ALK. Further we compared the mutation status with sex, age at diagnosis, stage, differentiation, smoking dose, and histological subtype.
RESULTS: Among 230 smokers, we detected 100 (43.5%) EGFR mutations, 38 (16.5%) KRAS mutations, 7 (3.0%) BRAF mutations and 7 (3.0%) EML4-ALK fusions. All mutations were mutually exclusive. No HER2 mutation was found. EGFR mutations occurred significantly more common in smokers with smoking dose ≤20 pack-years (p<0.001) or ≥60 years old at diagnosis (p=0.018). Smoking dose >20 pack-years and <60 years old at diagnosis were associated with the presence of KRAS mutation. With regard to association between histological subtypes and driver mutation status, EGFR mutation had positive correlation with micropapillary (p=0.003), lepidic (p=0.011), and papillary (p=0.05) predominant adenocarcinoma, and negative correlation with solid predominant(p<0.001) and invasive mucinous adenocarcinoma (IMA) (p=0.006). IMA had a positive correlation with KRAS mutation (p=0.043).
CONCLUSIONS: To our knowledge, this study represents the first comprehensive and concurrent analysis of these five well-identified driver mutations in a large cohort of lung adenocarcinoma from East-Asian smokers. Our molecular data in conjunction with the clinical and pathological features indicated that prospective genotyping of lung adenocarcinomas from smokers for these genetic alterations could lead to rationally chosen targeted therapy in the overwhelming majority of cases.
CLINICAL IMPLICATIONS: Our results indicate that the use of some targeted therapy of lung adenocarcinoma may be considered among some smokers with such clinical and pathological features. And it may help optimizing the design of further clinical trail.
DISCLOSURE: The following authors have nothing to disclose: Hang Li, Yunjian Pan, Lei Shen, Yuan Li, Chenguang Li, Rui Wang, Haichuan Hu, Ting Ye, Yang Zhang, Lei Wang, Yihua Sun, Haiquan Chen
No Product/Research Disclosure InformationFudan University Shanghai Cancer Center, Shanghai, China