MAGE-A1 expression is associated with good prognosis in neuroblastoma tumors.

Purpose: Neuroblastoma is an embryonal tumor of neuroectodermal cells. Patients with metastatic neuroblastoma have a poor survival rate, which has led to numerous efforts to develop prognostic markers. Cancer/testis-specific antigens MAGE-A1 and MAGE-A3 genes were proposed as minimal residual disease (MRD) markers in neuroblastoma, but its usefulness for this purpose is rather limited.
Methods: We studied 47 primary neuroblastoma tumors. RNA was extracted and cDNA was prepared by reverse transcription. Detection of the MAGE-A1 expression was done by hybridization of the RT-PCR products. We used methylation-specific-PCR to perform the epigenetic studies.
Results: We studied the MAGE-A1 and MAGE-A3 expressions, and the MAGE-A1 expression showed significant association with tumor stage, absence of bone marrow infiltration and survival. A multivariate analysis enabled us to conclude that the MAGE-A1 expression represents a new independent predictive factor, which is independent of N-Myc amplification (P value = 0.000), age at diagnosis (P value = 0.002) or tumoral stage (P value = 0.024). Considering the epigenetic regulation of MAGE-A1, we analyzed its methylation profile, and found a significant association with its expression in tumor cells. Moreover, we found tumors that failed to show the MAGE-A1 expression despite the hypomethylated sequence, and corresponded to advanced neuroblastoma that might share another mechanism involved in MAGE-A1 silencing. Given the association described between genome-wide hypomethylation and microsatellite instability, we determined the MSI status of tumor samples, finding a significant correlation with the MAGE-A1 expression and, more specifically, with the hypomethylated status of this gene only in female patients.
Conclusion: We conclude that the MAGE-A1 expression is associated with good prognosis in neuroblastoma.