Epstein Barr Virus, p53 and bcl-2 expression in pediatric lymphoma: their prognostic value in a follow up analysis

PAOLA ANDREA CHABAY; DE MATTEO, E; REY, G.; FREIGEIRO, D.; AVERSA, L.; PRECIADO, M. V.

Ginebra

Congreso; 38 th International Society of Pediatric Oncology Congress; 2006

Context: Epstein Barr virus (EBV) is an ubiquitous herpes virus with a 95% world wide seroprevalence.  Primary infection is usually asymptomatic in childhood, and persists for life in B cell. EBV is associated with a variety of human malignancies including Burkitt’s lymphoma, post-transplant lymphoproliferative disease and Hodgkin’s lymphoma (HL). There is evidence that lymphomagenesis also involves alteration in pathways responsible for controlling both cell cycle and apoptosis machinery; being p53 and bcl-2 the best studied ones. Our aim was to assess EBV, p53 and bcl-2 expression in pediatric lymphoma and to correlate it with patient’s event free survival. Methods: 174 pediatric lymphoma cases (111 HL and 63 non Hodgkin lymphoma [NHL]) from 1990 to 2005 were selected from the archives of the Pathology Service at Ricardo Gutierrez Children’s Hospital on the basis of available formalin-fixed paraffin-embedded lymph node biopsies. EBERs in situ hibridization was performed for EBV evaluation, and in a subset of 131 cases p53, bcl-2 were determined by immunohistochemistry. Results: EBER expression was detected in 77/174 (44.3%) lymphomas (27.4% NHL and 54% HL).Particularly, EBV was observed in 75/147 (51%) B-cell vs 2/21 (9.5%) T-cell lymphomas. P53 and bcl-2 showed positive staining in 108/131 (82.4%) and 57/131 (43.5%) cases, respectively.  Kaplan Meier survival analysis showed that neither p53 nor bcl-2 expression correlated with event free survival in this lymphoma series.  Meanwhile, EBV expression was associated with worse event free survival only in NHL (p=0.0019, long rank test). Conclusions: EBV could be involved in pediatric lymphomagenesis as a cofactor, particularly in B-cell lymphoma development. Nevertheless, its expression has only a significant correlation with patient’s outcome in pediatric NHL. On the other hand, even though high p53 overexpression seems to play a key role in neoplasic transformation, neither p53 nor bcl-2 could be used to predict patient’s survival.