Association of low expression of VEGF121 soluble isoform with prognostic impact and survival in patients with activated B-cell-like (ABC-like) diffuse large B-cell lymphoma (DLBCL) from the CORAL trial.

Abstract

8048 Background: Gene expression profiling (GEP) has demonstrated that survival of DLBCL is influenced by the origin of the tumor cells (COO), germinal center-like (GC-like) vs ABC-like (Alizadeh et al. 2000), but also by the tumor microenvironment, particularly the angiogenesis (Lenz et al., 2008). To further understand the prognostic impact of these tumoral characteristics, we analysed the prognostic impact of COO and the expression of biomarkers involved in angiogenesis, in a selected population of 36 patients with relapsed/refractory DLBCL included in CORAL (Gisselbrecht, ASCO 2011). Methods: Expression of 5 biomarkers including VEGF (isoforms 121, 165, and 189), and their receptors (VEGFR-1 and R-2) was assessed by quantitative qRT-PCR after total RNA extraction and cDNA synthesis of tumor samples. COO was determined by GEP, and progression free- (PFS) and overall- (OS) survivals were analysed. Results: In the study population, VEGF121 expression below the median was associated to a better outcome, with 4 year-PFS at 63% vs 33% (p=.053), and a 4-year-OS at 79% vs 37% (p = 0.032), respectively. VEGF-165 -189, VEGF-R1, -R2 did not have any significant impact. Eighteen patients were predicted as ABC-like DLBCL and 18 as GCB-like DLBCL. In patients with ABC-like DLBCL, low VEGF121 level was associated to a significantly better survival than in those with high VEGF121 level: 4-year OS at 100% vs 36% (p=.011). The type of induction treatment, R-ICE or R-DHAP, did not influence the outcome. The differences in outcome according to VEGF isoforms were not significant among CGB patients. Conclusions: Our data suggest that angiogenesis plays a central role in ABC-like DLBCL. VEGF121 seemed to be a key player in this context and should be proposed as a target in the treatment of patients with ABC-like DLBCL.