P52 Activation in Monomorphic B-Cell Post-Transplant Lymphoproliferative Disorders without BAFF-R Expression.

Abstract 2932

Poster Board II-908

Post-transplant lymphoproliferative disorders (PTLD) are one of the worse prognostic complications after solid organ or bone marrow stem cells transplantation. Most of them are associated to EBV known to activate NF-kB pathway especially by constitutive p65 expression. BAFF cytokine, a B cell-activating factor belonging to the tumour necrosis factor (TNF) family, have been described to modulate cell growth and survival in non Hodgkin lymphomas. However, little is known on the association between EBV, BAFF/BAFF-R signalling and canonical and non canonical NF-kB pathways expression in PTLD. Thus, we intend to study the role of EBV, NF-κB and BAFF/BAFF-R expression in PTLD.Our study has been investigated in two different contexts of diffuse large B-cell lymphoma (DLBCL). 20 cases of DLCBL resulting from immunocompetent patients (DLBCL/IC) and 13 from post-transplant recipients (DLBCL/PTLD) were compared. Indeed, all cases were characterized by histology and immunohistochemistry (IHC) was used to detect B-cell markers and to identify their germinal center (GC) or non GC (NGC) origin. EBV was detected by in situ Hybridisation (ISH) using EBER probe. Latent proteins LMP1 and EBNA2 as well as replicative protein ZEBRA were also detected by IHC. In addition, p50 and p52 proteins expression was carried out to study NF-kB pathway activation.

We showed in DLBCL/IC, regardless of the ontogenic profile GC/NGC, that BAFF-R is expressed in 40% of cases, while in DLBCL/PTLD NGC pattern, BAFF-R is expressed in only one case out of 13 (7,7%) (p<0,05). Moreover, there was no significant difference in p50 expression between the categories of DLBCL studied. In contrast, we have shown a significant expression of p52 in DLBCL/PTLD (8 out of 13 cases) compared to DLBCL/IC (4 out of 20 cases) (p<0.005). In DLBCL/PTLD, there was no expression of BAFF-R ; this pattern could be related to the presence of EBV and LMP1 since p52 expression is mostly observed in EBV+ DLBCL/PTLD (5 out of 7 p52+ cases).

In conclusion, the activation profile of DLBCL/PTLD is mostly not associated with BAFF/BAFF-R expression while NF-kB2 pathway is activated.