High frequency of Epstein Barr Virus Latent Membrane Protein-1 30 bp deletion in a series of pediatric malignancies

PAOLA ANDREA CHABAY; DE MATTEO, E; PRECIADO, M. V.

Archives of Virology

Springer Verlag

Año: 2004 vol. 149 p. 1515 - 1526

0304-8608

Introduction: 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 immunohistochemistry, 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. As controls, 8 fresh normal lymphoid tissue samples and 3 peripheral blood lymphocytes 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.