Xu-Monette, Zijun Y3; Wu, Lin3; Visco, Carlo3; Tai, Yu Chuan3; Tzankov, Alexander3; Liu, Wei-Min3; Montes-Moreno, Santiago3; Dybkær, Karen5; Chiu, April3; Orazi, Attilio3; Zu, Youli3; Bhagat, Govind3; Richards, Kristy L3; Hsi, Eric D3; Zhao, X Frank3; Choi, William Wl3; Zhao, Xiaoying3; van Krieken, J Han3; Huang, Qin3; Huh, Jooryung3; Ai, Weiyun3; Ponzoni, Maurilio A3; Ferreri, Andres Jm3; Zhou, Fan3; Kahl, Brad S3; Winter, Jane N3; Xu, Wei3; Li, Jianyong3; Go, Ronald S3; Li, Yong3; Piris, Miguel A3; Møller, Michael B3; Miranda, Roberto N3; Abruzzo, Lynne V3; Medeiros, L Jeffrey3; Young, Ken H3
1 Department of Clinical Medicine - Hæmatologisk Afdeling, Aalborg Sygehus, Department of Clinical Medicine, Health, Aarhus University2 Department of Clinical Medicine - Kirurgisk Gastroenterologisk afdeling A, AAL, Department of Clinical Medicine, Health, Aarhus University3 unknown4 Department of Clinical Medicine, Health, Aarhus University5 Department of Clinical Medicine, Health, Aarhus University
a report from an International DLBCL Rituximab-CHOP Consortium Program study
TP53 mutation is an independent marker of poor prognosis in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (CHOP) therapy. However, its prognostic value in the rituximab immunochemotherapy era remains undefined. In the present study of a large cohort of DLBCL patients treated with rituximab plus CHOP (R-CHOP), we show that those with TP53 mutations had worse overall and progression-free survival compared with those without. Unlike earlier studies of patients treated with CHOP, TP53 mutation has predictive value for R-CHOP-treated patients with either the germinal center B-cell or activated B-cell DLBCL subtypes. Furthermore, we identified the loop-sheet-helix and L3 motifs in the DNA-binding domain to be the most critical structures for maintaining p53 function. In contrast, TP53 deletion and loss of heterozygosity did not confer worse survival. If gene mutation data are not available, immunohistochemical analysis showing > 50% cells expressing p53 protein is a useful surrogate and was able to stratify patients with significantly different prognoses. We conclude that assessment of TP53 mutation status is important for stratifying R-CHOP-treated patients into distinct prognostic subsets and has significant value in the design of future therapeutic strategies.