Frequent expression of MAGE tumor antigens in bronchial epithelium of chronic smokers without lung cancer

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA 1692 Background : Melanoma antigens ( MAGE ) type 1are considered tumor-specific antigens and potential targets for cancer management. We have earlier shown that MAGE -A1, -A3, and -B2 genes frequently express in patients of non-small cell lung cancers (NSCLCs). Importantly, these genes also expressed in the adjacent normal lungs of these patients raising the possibility that activation of MAGE occurs in carcinogen-exposed bronchial epithelial cells. The purpose of current study was to test the hypothesis that MAGE activation is an important event in lung carcinogenesis and occurs early enough in the bronchial epithelium to be used as a potential biomarker for lung cancer prevention studies. Methods: We tested MAGE -A1, -A3, and -B2 genes expression profiles in bronchial brush samples from chronic smokers, enrolled on a lung chemoprevention clinical trial, by reverse transcription- PCR (RT-PCR). Bronchial brush samples were obtained from six different sites per individual. We analyzed the expression profiles with clinicopathologic parameters using both patients (expression index of six bronchial brush sites of each patient) and the bronchial brush sites as separate analytic units. Results: The median age of the 66 subjects was 54 yr (range 32-73 yr), including 17 former smokers (who stopped smoking for more than 12 months) and 49 current smokers, and had a median of 38 pack-years smoking history. Among the 66 chronic smokers, 37 (56%), 50 (76%), and 25 (38%) had detectable MAGE -A1, -A3, and -B2 expression, respectively in at least one of the bronchial brushing sites. Of the total 391 bronchial brush specimens tested, MAGE -A1, -A3, and -B2 expression was detected in 61 (16%), 103 (26%), and 43 (11%) respectively. More importantly, as compared to former smokers, significantly higher proportion of current smokers had positive expression of MAGE A1 (35% Vs 63%, P = 0.045). On further analysis with GEE model on MAGE expression, using the site (nested in participant) as a unit, we found that significantly higher proportion of sites in current smokers ( P = 0.04) had positive expression of MAGE - A1 adjusted for age and MAGE B2 ( P = 0.02) adjusted for pack-years. Conclusions: MAGE -A1, -A3, and -B2 genes are frequently expressed in bronchial epithelium of chronic smokers without the evidence of lung cancer, suggesting that smoking activates MAGE genes. Smoking cessation might reduce the incidence of expression of these genes. These findings, together with the fact that such genes are not expressed in normal lungs and have an important role in lung cancer growth regulation, suggest that these molecules may serve as biomarkers in early detection and/or surrogate endpoints for lung chemoprevention trials.