Abstract 787: Differences in protein expression patterns in lung adenocarcinomas arising in never versus ever smokers

Background. Approximately 25% of lung cancer cases worldwide, mostly adenocarcinomas, are not attributable to tobacco use. Despite that some striking differences have been identified in the epidemiological, clinical and molecular characteristics of lung cancer arising in never smokers versus smokers, our current knowledge of lung adenocarcinoma in never smokers is still limited. Methods. We examined the immunohistohemical (IHC) expression of 101 proteins in surgically resected lung adenocarcinoma tissue microarray specimens obtained from 52 never smokers and compared the findings with 152 tumors obtained from ever smokers. The markers examined included a wide variety of tumor-related proteins, representing all hallmarks of cancer (Hanahan and Weinberg, Cell 2000). The IHC expression was assessed at cytoplasm [c], membrane [m], and nucleus [n] of malignant cells, and in stromal cells. Univariate and multivariate (adjusting by patients’ sex, and tumor stage and EGFR mutation status) statistical analyses were performed to assess the statistical differences in the expression of markers according to smoking status. The expression of the markers was correlated with patients’ clinical characteristics and tumors’ pathological features and EGFR mutational status. Results. In the multivariate analysis, tumors from smokers showed a relatively high number of markers (n=32) with significant higher expression compared with tumors from never smokers. Interestingly, in the univariate analysis, nine markers showed significantly higher expression in tumors from never smokers compared with ever smokers, including FGFR-1 [n], FGFR-2 [n], ER-alpha [n], CD44 [c], FOLR1 [m], IGFBP3 [n], IL-1alpha [c], NF-kB [n], survivin [n] and RGS17 [n]. In the multivariate analysis, six markers showed significantly higher expression in tumors from never smokers, including FGFR-2 [n] (P=0.018), CD44 [c] (P=0.001), c-Met [c] (P=0.045) and [m] (P=0.017), E-Cadherin [m] (P=0.003), IGFBP3 [n] (P=0.0009) and p-HER3 [m] (P=0.035). Twenty-nine markers showed significant association with EGFR mutations in tumors in the multivariate analysis adjusting by patients’ sex and smoking status, and tumor stage. Additionally, 47 markers showed significant differences in the level of expression comparing patients’ smoking status, including current, former and never smokers. Conclusion. Our findings indicate that there are multiple molecular differences between lung adenocarcinomas arising in never and ever smokers, suggesting that they are different entities. These findings have implications for the selection of molecular targets for developing novel therapy in patients with lung adenocarcinoma based on their smoking history (Supported by grant VITAL W81XWH-04-1-0142 and UT-Lung SPORE P50CA070907). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 787.