Analysis of the Epstein Barr virus involvement in the pathogenesis of diffuse B cell lymphoma and its interaction with the tumor microenvironment

COHEN, M; VISTAROP A; NARBAITZ, M; METREBIAN, F; DE MATTEO E; PRECIADO MV; PAOLA ANDREA CHABAY

Trieste

Congreso; ICGEB DNA tumour virus meeting 2015; 2015

ICGEB

EBV-positive diffuse large B-cell lymphoma (EBV+ DLBCL) of the elderly is a provisional entity included in the 2008 WHO classification of lymphoid tumors that occurs in immunocompetent patients older than 50 years old. It was proposed that it is related to the senescence of the immune system inherent to the aging process. Current literature does not establish a definitive EBERs cutoff to define a DLBCL case as EBV+. Our aim was to study the role of EBV in DLBCL pathogenesis in pediatric, young and older patients from our country and to characterize tumor microenvironment. One-hundred and two DLBCL cases were collected. EBERs in situ hybridization and immunohistochemistry for EBNA2, EBNA3A, LMP1, LMP2A and BMRF1 viral antigens and CD4, CD8, Foxp3, GrB and PD-1 cell markers were performed. EBV gene expression, TGF, IL-10, IFN and CCL-20 transcripts were measured using real-time PCR. EBV+ and - cases from all age-groups were compared. EBV+ DLBCL frequency was similar in all age-groups using more than 20% EBERs+ tumor cells as a cutoff value; the viral latency patterns II and III together with lytic expression were prevalent. PD-1 was predominant in all cases of DLBCL, while GrB+ cells were markedly increased in EBV+ DLBCL cases, in which a trend to lower event-free survival was noticed. In conclusion, EBV+ DLBCL may be an entity that is not only restricted to patients who are older than 50 years of age, in consequence the revision of age cutoff may be a current goal.