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MAGE-A3 Expression is an Independent Determinant of Worse Survival in Stage IA Non-Small Cell Lung Cancer
Jeffrey L. Port1, Sacha Gnjatic2, Otavia Caballero2, Ramon Chua2, Achim A. Jungbluth2, Gerd Ritter2, Cathy A. Ferrara1, Paul C. Lee1, Lloyd J. Old2, Nasser K. Altorki1; 1Weill Cornell Medical College/NY Presbyterian Hospital, New York, NY; 2Ludwig Institute for Cancer Research, New York, NY
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Objective: MAGE-A3 is a tumor specific antigen that belongs to the cancer -testis (CT) gene family. MAGE- A3 is expressed in 40-50% of non-small cell lung cancer (NSCLC) and its expression is negatively correlated with survival. Members of the CT antigen family are considered ideal targets for tumor immunotherapy and a randomized trial is currently underway to evaluate the efficacy of MAGE-A3 vaccination in the adjuvant setting for stage IB-IIIA NSCLC (MAGRIT). However, no information is available about the expression of MAGE- A3 in early stage disease. In this study we examined the expression of MAGE-A3 in patients with resected IA disease using tumor tissues from an institutional tissue bank linked to a prospectively established clinical database.
Methods: Fresh tumor tissue was obtained at surgery from stage IA patients who underwent curative resection (1996-2008) without preoperative therapy. Total RNA was extracted for semiquanitiative RT-PCR. Univariate analysis was performed using the Wilcoxon rank sum and the chi-square test, as appropriate. The effect of expression on overall survival (OS) was evaluated using the Kaplan-Meier method and differences between groups compared by the log-rank test. The independent impact of MAGE-A3 expression on survival was calculated using a multivariable Cox regression model. Informed consent for tissue banking was obtained and the current study was approved by the IRB and patient consent was waived.
Results: 195 stage IA patients (117 female) with a median age of 69, a median tumor size of 2.0 cm, and a median follow-up of 3.8 years were analyzed. Positive MAGE -A3 expression was seen in 56% of patients and was significantly correlated with male gender (p=0.013), a history of smoking (p=0.05), and squamous histology (p<0.0001) . 5-year OS for the entire group was 75.8%. 5-yr OS for MAGE + vs MAGE - patients was 69.1% vs 83.0%, respectively (p=0.008) (FIGURE). A multivariate Cox regression analysis for OS determined male gender (hazard ratio [HR] 2.13, p=0.01) and MAGE expression (HR 2.32, p=0.01) to be significant negative predictors of survival.
Conclusion: This study identified MAGE expression as a significant negative prognostic factor for survival among stage IA NSCLC patients. In addition there appears to be a link between MAGE expression and male gender, squamous histology, and a previous history of smoking. These results provide a rationale for immunotherapy in stage IA NSCLC patients where standard cytotoxic therapy is not justified.


P=0.0080 by log-rank test.
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