Background: Simian virus 40 (SV40) is an oncogenic DNA virus which is an emergent pathogen implicated in some human malignancies, including B-cell lymphomas. However, previous studies of SV40 and human lymphomas have searched only for viral DNA sequences and have been limited to the United States and Europe. Methods: Case-control study of lymphomas from adult HIV-negative patients diagnosed at two tertiary care centers from January 1999 to December 2002 in San Jose, Costa Rica. Case and control specimens that were masked were examined by polymerase chain reaction using primers specific for the amino and carboxy-terminal regions of the SV40 large tumor antigen (T-ag) gene. SV40 sequences were confirmed by both Southern blot and DNA sequence analysis. Specimens were also tested for herpesvirus EBV using specific primers for the Latent Membrane Protein 2a gene. In addition, samples were immunophenotyped and assessed for the expression of SV40 T-ag by immunohistochemistry (IHC). Results: One-hundred and fifteen lymphomas (NHL [n=96] and Hodgkin’s lymphomas [n=19] and 91 nonmalignant lymphoid (reactive lymph nodes and tonsils [n=51]) and cancer (gastric and hepatic carcinomas [n=40]) control cases were examined blindly. After decoding the identity of the samples, SV40 T-ag sequences were detected significantly more often in lymphomas than in control samples (26/115, 23% vs. 0/91, 0%; p=0.001). T-ag sequences were detected in 25% and 10% of NHL and Hodgkin’s lymphoma, respectively. SV40 sequences were detected only in B-cell neoplasms. EBV DNA was detected in 10% and 33% of lymphomas and control specimens. None of the lymphomas were positive for both SV40 and EBV. IHC showed expression of SV40 T-ag in 70% of the lymphomas found to contain T-ag DNA sequences and in none of the samples that were negative for viral DNA sequences. Expression of the viral oncoprotein was restricted to malignant cells and not to reactive lymphocytes. Conclusion: These results indicate that SV40 is significantly associated with adult B-cell neoplasms in Costa Rica. Expression of the viral oncoprotein suggests that SV40 may be etiologically meaningful in the development of some of these malignancies. Studies are needed to establish the prevalence, pathways of transmission, and populations at risk for SV40 infections.
[Proc Amer Assoc Cancer Res, Volume 45, 2004]