Epstein Barr virus expression and latency profile in pediatric Burkitt lymphoma: its correlation with apoptosis markers

LARA JULIA; DE MATTEO ELENA; LORENZETTI MARIO ALEJANDRO; AVERSA LUIS; PRECIADO MARIA VICTORIA; CHABAY PAOLA

Boston

Congreso; 42nd Congress of the International Society of Pediatric Oncology; 2010

International Society of Pediatric Oncology

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.