title: Lymphomas in patients with connective tissue disease. Comparison of p53 protein expression and latent EBV infection in patients immunosuppressed and not immunosuppressed with methotrexate.
abstract: Cell cycle dysregulation as measured by p53 protein expression and latent Epstein-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 who are immunosuppressed with methotrexate, p53 protein expression has not been reported. We compared the immunohistologic expression of p53 protein and the incidence of latent EBV infection in lymphomas arising in patients with connective tissue disease treated and not treated with methotrexate. Increased p53 staining was detected in 10 of 11 lymphomas arising in patients after methotrexate therapy vs 5 of 11 in patients not treated with methotrexate. 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5 of 7 lymphomas arising after treatment with methotrexate, including 1 that regressed after methotrexate therapy was withdrawn. These findings suggest that cell cycle dysregulation and EBV-related transformation are important in the pathogenesis of lymphomas arising in patients with connective tissue disease who are immunosuppressed with methotrexate.
authors.affiliation: Department of Pathology, Mayo Clinic Jacksonville, FL, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Menke
authors.forename: H
authors.initials: H
authors.lastname: Griesser
authors.forename: K G
authors.initials: KG
authors.lastname: Moder
authors.forename: A
authors.initials: A
authors.lastname: Tefferi
authors.forename: H S
authors.initials: HS
authors.lastname: Luthra
authors.forename: M D
authors.initials: MD
authors.lastname: Cohen
authors.forename: G
authors.initials: G
authors.lastname: Colon-Otero
authors.forename: R V
authors.initials: RV
authors.lastname: Lloyd
mesh_terms: D000293:Adolescent; D000328:Adult; D003240:Connective Tissue Diseases / Q000150:complications*; D020031:Epstein-Barr Virus Infections; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D017403:In Situ Hybridization; D008223:Lymphoma / Q000209:etiology* / Q000378:metabolism / Q000821:virology*; D008297:Male; D008727:Methotrexate / Q000009:adverse effects*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
chemical_list: D007166:Immunosuppressive Agents; D016159:Tumor Suppressor Protein p53; D008727:Methotrexate