Xu-Monette, Zijun Y5; Møller, Michael6; Tzankov, Alexander5; Montes-Moreno, Santiago5; Hu, Wenwei5; Manyam, Ganiraju C5; Kristensen, Louise5; Fan, Lei5; Visco, Carlo5; Dybkær, Karen7; Chiu, April5; Tam, Wayne5; Zu, Youli5; Bhagat, Govind5; Richards, Kristy L5; Hsi, Eric D5; Choi, William W L5; van Krieken, J Han5; Huang, Qin5; Huh, Jooryung5; Ai, Weiyun5; Ponzoni, Maurilio5; Ferreri, Andrés J M5; Winter, Jane N5; Wu, Lin5; Zhao, Xiaoying5; Go, Ronald S5; Wang, Sa A5; Bueso-Ramos, Carlos E5; Li, Yong5; Piris, Miguel A5; Medeiros, L Jeffrey5; Young, Ken H5
1 The Faculty of Medicine, Aalborg University, VBN2 Aalborg University Hospital, The Faculty of Medicine, Aalborg University, VBN3 Klinik Medicin, The Faculty of Medicine, Aalborg University, VBN4 Blodsygdomme (Hæmatologi), The Faculty of Medicine, Aalborg University, VBN5 unknown6 Klinisk Institut7 Department of Clinical Medicine, The Faculty of Medicine, Aalborg University, VBN
a report from the international DLBCL rituximab-CHOP consortium program
MDM2 is a key negative regulator of the tumor suppressor p53, however, the prognostic significance of MDM2 overexpression in diffuse large B-cell lymphoma (DLBCL) has not been defined convincingly. In a p53-genetically defined large cohort of de novo DLBCL patients treated with R-CHOP chemotherapy, we assessed MDM2 and p53 expression by immunohistochemistry (n=478), MDM2 gene amplification by fluorescence in situ hybridization (n=364), and a single nucleotide polymorphism in the MDM2 promoter, SNP309, by SNP genotyping assay (n=108). Our results show that MDM2 overexpression, unlike p53 overexpression, is not a significant prognostic factor in overall DLBCL. Both MDM2 and p53 overexpression does not predict for an adverse clinical outcome in patients with wild-type p53, but predicts for significantly poorer survival in patients with mutated p53. Variable p53 activities may ultimately determine the survival differences as suggested by the gene expression profiling analysis. MDM2 amplification was observed in 3 of 364 (0.8%) patients with high MDM2 expression. Presence of SNP309 did not correlate with MDM2 expression and survival. This study indicates that evaluation of MDM2 and p53 expression correlating with TP53 genetic status is essential to assess their prognostic significance, and important for designing therapeutic strategies that target the MDM2-p53 interaction.