Prognostic significance of cell proliferation and apoptosis-regulating proteins in epstein-barr virus positive and negative pediatric hodgkin and non-hodgkin's lymphoma

Apoptosis, proliferation and relationship with EBV is a contemporary issue in the pathogenesis of HL and NHL. Antiapoptotic bcl-2, proapoptotic bax, inhibitor of apoptosis protein survivin, extrensec apoptotic pathway receptor fas, tumor supressor gene product p53 are apoptosisrelated proteins. C-myc is an oncogene that plays a role in cell-cycle G1-S pass. Ki 67 is a proliferation marker expressed in G1, S, G2, M phases of cell-cycle. In this study prognostic or pathogenetic role of EBV, proliferating activity, apoptosis and regulating proteins in pediatric HL and NHL were explored. EBV-EBER, lmp-1, ki-67, Bcl-2, survivin, Bax, fas, c-myc, p53 and AI detected by in-situ TUNEL method were explored in.63 HL and 70 NHL cases Statistical evaluation was done by chisquare, Mann Whitney U test, Pearson Correlation and Kaplan Meier survival analysis. The mean age of HL cases was 8.46. Among 32 early and 31 advanced stage cases exitus was observed in four and relapse in six cases. Overall survival was 94% and event free survival 83.6%. EBV was positive in 82.5%, bax in 74.6%, bcl-2 in 47.6%, survivin in 43%, p53 in 33.3%, fas in 54% and c-myc in 25.4% cases. Mean AI was 18,22%. Mean proliferation index(PI) was 57,83%. EBV was positively related with PI and negatively with AI, not with bax, bcl-2, survivin, p53, fas and c-myc. None of the parameters were related with prognosis. The mean age of NHL cases was 7.16. Among seven early stage and 63 advenced stage cases exitus was observed in 10 cases and relapse in four cases. Overall survival was 82%, while event free survival was 75%. EBV was positive in 25.7%, bax in 40%, bcl-2 in 50%, survivin in 42,9%, p53 in 8,6%, fas in 18,6% ve c-myc 45,7%. Mean AI was 131,29/5000 cells, mean PI was 55,97%. EBV was related with fas and negatively related with bcl-2, not ralated by other factors. None of the parameters were related with prognosis. Our results suggest that EBV might play a role in HL pathogenesis by inducing proliferative activity and by inhibiting apoptosis but does not predict prognosis. Our results of pediatric NHL series indicate that EBV does not have a primary role in the pathogenesis.