High frequency of Epstein Barr virus latent membrane protein-1 30?bp deletion in a series of pediatric malignancies in Argentina

Abstract

Epstein Barr virus widely infects human populations and remains mostly asymptomatic; however, it has been associated with several malignancies. The EBV-encoded latent membrane protein-1 has been involved in neoplasic transformation; a 30-bp deletion and several mutations in the COOH-terminal domain have been associated with histopathological and clinical disease features. Objective: To analyze and correlate the presence of mutations and a 30-bp deletion with the influence of LMP-1 on tumorigenicity in a population of EBV+ pediatric malignancies. Methods: We studied EBV presence by LMP-1 immunohistoche- mistry, EBERs in situ hybridization and PCR in fresh and formalin-fixed paraffin-embedded tissue samples from 10 Hodgkin’s lymphomas, 6 non-Hodgkin’s lymphomas, 4 undifferentiated nasopharyngeal carcinomas. Eighteen out of 20 samples were sequenced. Eight fresh normal lymphoid tissue samples and 3 peripheral blood samples were analyzed. Results: All cases were EBV positive. EBV typing rendered 12 EBV-1 and 8 EBV-2. Del-LMP-1 was detected in 15/20 EBV related malignancies, as well as in 4/11 control tissues. A high percentage of patients showed point mutations previously described. The presence of del-LMP-1 and point mutations failed to correlate with clinical course. Conclusions: We found a marked incidence of del-LMP-1 (75%) in our series. However, we failed to find any correlation between histological aggressiveness of malignancies and the presence of del-LMP-1 and point mutations.