Lymphomas in patients with connective tissue disease - Comparison of p53 protein expression and latent EBV infection in patients immunosuppressed andnot immunosuppressed with methotrexate

Cell cycle dysregulation as measured by p53 protein expression and latent E pstein-Barr (EBV) infection are important in the pathogenesis of lymphoma, particularly in immunosuppressed patients. Although latent EBV commonly is detected in lymphomas arising in patients with connective tissue disease wh o are immunosuppressed with methotrexate, p53 protein expression has not be en reported. We compared the immunohistologic expression of p53 protein and the incidence of latent EBV infection in lymphomas arising in patients wit h connective tissue disease treated and not treated with methotrexate. Incr eased p53 staining was detected in 10 of 11 lymphomas arising in patients a fter methotrexate therapy vs 5 of 11 in patients not treated with methotrex ate. Latent EBV was detected in 7 of 13 lymphomas arising in patients after methotrexate therapy vs 2 of 11 in patients not treated with methotrexate. Concordant p53 expression and latent EBV were detected in 5 of 7 lymphomas arising after treatment with methotrexate, including 1 that regressed afte r methotrexate therapy was withdrawn. These findings suggest that cell cycl e dysregulation and EBV-related transformation are important in the pathoge nesis of lymphomas arising in patients with connective tissue disease who a re immunosuppressed with methotrexate.