Epstein Barr Virus expression and latency profile in pediatric Burkitt lymphoma. Its correlation with apoptosis markers

LARA J; DE MATTEO E; LORENZETTI M; AVERSA L; PRECIADO MV; CHABAY P

Boston

Congreso; 42 Meeting of International Society of Pediatric Oncology; 2010

There are three epidemiological forms of Burkitt Lymphoma (BL) according to Epstein Barr virus (EBV) association. The “endemic”, in children in areas with holoendemic malaria, is 100% EBV+. The “sporadic”, mainly in children, is 15%-20% EBV+ in Western countries and with a higher EBV association in locations like equatorial Brazil. The “AIDS-BL”, in HIV-infected individuals, is 30%-40% EBV+. Objective: To characterize EBV association and latency pattern in a pediatric BL population from Argentina, and to correlate this with apoptosis markers. Methods: We analyzed 28 BL pediatric patients (3 HIV+), age range 1 to 16 ys (median: 5ys), male:female ratio 17:11. EBV expression was evaluated by EBERs in situ hybridization, and aCasp3, bax and bcl2 expression was assessed by immunohistochemistry in formalin fixed-paraffin embedded lymph node biopsies. RNA extraction was performed with Qiagen RNAeasy FPPE kit, and in RNA+ samples, EBV RNA expression was characterized by RT-PCR for EBERs, LMP1, LMP2A, BZLF1 and BHRF1. Results:  Ten out 28 of cases (35.7%) were EBERs positive, 7 immunocompetent (28%) and 3 HIV+ patients (100%). EBV expression was not statistically associated with aCasp3, bax and bcl2 positive staining. EBV latency pattern was EBERs+, LMP1-, LMP2A-, BZLF1- and BHRF1-. Even though, in Kaplan Meier survival analysis, 5 ys event-free survival (EFS) in EBV+ cases was 42%, lower than 79% observed in EBV- cases, this different was not statiscally significant (p=0.1431, log rank test).  Conclusion:  EBV expression in immunocompetent patients showed the “sporadic” pattern described in Western population, and in the immunocompromised ones, a 100% of EBV expression, higher than the observed in AIDS-BL.  We described a type I latency pattern.  EBV presence did not alter the apoptotic pathway analyzed.  Further analysis with a larger series of pediatric patients will be needed to confirm the trend to a worse 5ys EFS observed in EBV+ patients.