Abstract 3533: Clinical impact of NF-KB activation in diffuse large B cell lymphoma.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Deregulated nuclear factor KB (NF-KB) activity has been associated with a number of lymphoproliferative diseases, including diffuse large B cell lymphoma (DLBCL), but the importance and consequence of this activation are still not fully understood. In this study, we describe the extent of NF-KB activation in a range of human lymphoma types and observe a frequent concurrent activation of both classical and alternative pathways in DLBCL. The activation of the classical and alternative NF-KB pathways, was present in 34.8% and 29.3% of DLBCL cases respectively, as assessed by nuclear expression of p50 (classical pathway) and p52 (alternative pathway) by immunohistochemistry in a series of 167 samples. Activation of NF-KB was observed in both germinal centre B-cell like (GC) and activated B-cell like (ABC) subtypes, although with a predominance of classical NF-KB in the ABC subtype (41,8% positive cases versus 21,2% in the GC subtype). In our cohort of samples from 167 R-CHOP treated DLBCL patients, excluding cases positive for Epstein-Barr virus, nuclear expression of NF-KB was significantly associated with a superior overall survival (Log Rank p<0.05), as compared to those without nuclear NF-KB. The 3-year overall survival rate in the NF-KB positive group was 83.6% compared to 68.0% in the NF-KB negative group. While p50 expression alone did not give rise to any significant differences in the survival curves, p52 expression did associate significantly with better clinical outcome (p=0.032). Thus, alternative NF-KB activation is frequently present in DLBCL tumors, is not associated with the ABC subtype, and is characterized by an enhanced overall survival. Citation Format: Lina Odqvist, Santiago Montes-Moreno, Margarita Sanchez-Beato, Lydia Sanchez-Verde, Manuela Mollejo, Ken H. Young, Manuel F. Fresno, Francisco Mazorra, Carmen Ruiz-Marcellan, Miguel A. Piris. Clinical impact of NF-KB activation in diffuse large B cell lymphoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3533. doi:10.1158/1538-7445.AM2013-3533