Prognostic value of MAGE-A3 and PRAME gene expression in non-small-cell lung cancer (NSCLC).

Abstract

7056 Background: We investigated the expression of some cancer–testis genes and their association with disease prognosis. Here we report our results for the expression, in resected NSCLC samples, of two tumor-specific antigens (Ags): MAGE‑A3 and PRAME, both under evaluation in clinical trials. Methods: We conducted a single-center, uncontrolled, retrospective study of tissue from resected stage I–III NSCLC patients (pts): 650 were in stage I, 215 in stage II and 395 in stage III. 1260 FFPE tumor tissue samples from the tumor tissue bank of the Department of Pathology, Lungenklinik Hemer (Germany), were tested for MAGE‑A3 and PRAME expression by specific qRT-PCR assays. The prognostic value of these Ags was determined by estimating the median overall survival (OS), disease-free interval (DFI) and disease-free survival (DFS). Results: Expression rates were 36% for MAGE‑A3 and 66% for PRAME. The co‑expression rate was 30%. Almost all tumors expressing MAGE‑A3 also expressed PRAME. We observed no difference overall in Ag expression according to stage, tumor size and pts’ age. Squamous tumors expressed MAGE‑A3 and PRAME more frequently than did adenocarcinomas (43 vs. 27 % and 80 vs. 44% respectively), and PRAME expression rates were higher in males than in females (70 vs. 53%). In the overall population, which included stages IA–IIIB, no prognostic value was detected for the expression of either Ag. In subset analyses, we found in 83 stage IIIB pts a trend to worse OS linked to MAGE‑A3 expression (HR=1.977, p=0.0312). In 395 stage IB pts, PRAME expression was associated with worse OS (HR=1.483, p=0.0344) and DFS (HR=1.492, p=0.0167). Conclusions: The MAGE‑A3 expression rate found is consistent with the results observed in the phase III MAGRIT trial (J‑H Kim et al., 2011). No prognostic value for either PRAME or MAGE‑A3 was observed in the overall population, in contrast to previous reports with smaller sample sizes (Gure et al., 2005, Boli et al., 2002) and in other tumors (Vourch’jourdain et al., 2009, Epping et al., 2008). We observed a trend toward poor prognostic value of MAGE‑A3 in stage IIIB pts and of PRAME in stage IB pts.