1. Evaluation of NF-κB subunit expression and signaling pathway activation demonstrates that p52 expression confers better outcome in germinal center B-cell-like diffuse large B-cell lymphoma in association with CD30 and BCL2 functions
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Jooryung Huh, Ling Li, Ganiraju C. Manyam, Ken H. Young, Santiago Montes-Moreno, Andrés J M Ferreri, Huilan Rao, William W.L. Choi, Carlo Visco, Mark J. Routbort, Govind Bhagat, Michael Boe Møller, Jane N. Winter, Zijun Y. Xu-Monette, April Chiu, Maurilio Ponzoni, Ben M. Parsons, Kristy L. Richards, Sa A. Wang, Youli Zu, Karen Dybkær, L. Jeffrey Medeiros, Eric D Hsi, J. Han van Krieken, Li Zhang, Attilio Orazi, Chi Young Ok, Alexandar Tzankov, Miguel A. Piris, Ok, Chi Young, Xu-Monette, Zijun Y, Li, Ling, Manyam, Ganiraju C, Montes-Moreno, Santiago, Tzankov, Alexandar, Visco, Carlo, Dybkær, Karen, Routbort, Mark J, Zhang, Li, Chiu, April, Orazi, Attilio, Zu, Youli, Bhagat, Govind, Richards, Kristy L, Hsi, Eric D, Choi, William W L, van Krieken, J Han, Huh, Jooryung, Ponzoni, Maurilio, Ferreri, Andrés J M, Parsons, Ben M, Rao, Huilan, Møller, Michael B, Winter, Jane N, Piris, Miguel A, Wang, Sa A, Medeiros, L Jeffrey, and Young, Ken H
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Adult ,Male ,Pathology ,medicine.medical_specialty ,P50 ,Lymphoma ,CD30 ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,Kaplan-Meier Estimate ,Biology ,Fluorescence ,Disease-Free Survival ,Pathology and Forensic Medicine ,NF-kappa B p52 Subunit ,immune system diseases ,hemic and lymphatic diseases ,parasitic diseases ,Gene expression ,Large B-Cell ,medicine ,Humans ,neoplasms ,In Situ Hybridization ,In Situ Hybridization, Fluorescence ,Aged ,Proportional Hazards Models ,RELB ,NF-kappa B ,Germinal center ,Middle Aged ,medicine.disease ,Diffuse ,Immunohistochemistry ,Gene expression profiling ,Proto-Oncogene Proteins c-bcl-2 ,Tissue Array Analysis ,CD30 Ligand ,Female ,Lymphoma, Large B-Cell, Diffuse ,Signal Transduction ,Transcriptome ,Germinal center B-cell like diffuse large B-cell lymphoma - Abstract
Contains fulltext : 155215.pdf (Publisher’s version ) (Closed access) Nuclear factor-kappaB (NF-kappaB) is a transcription factor with a well-described oncogenic role. Study for each of five NF-kappaB pathway subunits was only reported on small cohorts in diffuse large B-cell lymphoma (DLBCL). In this large cohort (n=533) of patients with de novo DLBCL, we evaluated the protein expression frequency, gene expression signature, and clinical implication for each of these five NF-kappaB subunits. Expression of p50, p52, p65, RELB, and c-Rel was 34%, 12%, 20%, 14%, and 23%, whereas p50/p65, p50/c-Rel, and p52/RELB expression was 11%, 11%, and 3%, respectively. NF-kappaB subunits were expressed in both germinal center B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL, but p50 and p50/c-Rel were associated with ABC-DLBCL. p52, RELB, and p52/RELB expressions were associated with CD30 expression. p52 expression was negatively associated with BCL2 (B-cell lymphoma 2) expression and BCL2 rearrangement. Although p52 expression was associated with better progression-free survival (PFS) (P=0.0170), singular expression of the remaining NF-kappaB subunits alone did not show significant prognostic impact in the overall DLBCL cohort. Expression of p52/RELB was associated with better overall survival (OS) and PFS (P=0.0307 and P=0.0247). When cases were stratified into GCB- and ABC-DLBCL, p52 or p52/RELB dimer expression status was associated with better OS and PFS (P=0.0134 and P=0.0124) only within the GCB subtype. However, multivariate analysis did not show p52 expression to be an independent prognostic factor. Beneficial effect of p52 in GCB-DLBC appears to be its positive correlation with CD30 and negative correlation with BCL2 expression. Gene expression profiling (GEP) showed that p52(+) GCB-DLBCL was distinct from p52(-) GCB-DLBCL. Collectively, our data suggest that DLBCL patients with p52 expression might not benefit from therapy targeting the NF-kappaB pathway.
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- 2015