title: Infiltration of Epstein-Barr virus-harboring lymphocytes occurs in a large subset of bladder cancers.
abstract: OBJECTIVE
  Epstein-Barr virus (EBV) has been implicated in the genesis of a variety of human cancers. We aimed to confirm the presence and define the role of EBV in bladder cancer.
  
  
  METHODS
  A total of 39 bladder cancer specimens were analyzed. Ten urinary bladder tissues obtained at autopsy were used as a normal control. EBV-encoded RNA (EBER) was evaluated by in situ hybridization (ISH). Frozen material available from 18 EBER-positive cases was analyzed by using reverse transcription-polymerase chain reaction for BZLF1, an early lytic gene product. The expression of CD20, CD3, ZEBRA (BZLF1 product) and transforming growth factor beta1 (TGFbeta-1) was assessed using an immunohistochemical technique.
  
  
  RESULTS
  Infiltration of EBER-expressing lymphocytes was detected in 26 of 39 bladder cancer cases (66.7%). A small fraction of the tumor cells as well as the infiltrating lymphocytes were positive in two cases. All normal urinary bladder specimens showed negative results. The incidence of EBV-positive lymphocyte infiltration was significantly higher for advanced stage cancers than those in earlier stages (Ta-152% vs T2-4 93%, P = 0.013). The presence of BZLF1 mRNA was demonstrated in seven out of the 18 EBER-positive cases.
  
  
  CONCLUSIONS
  Infiltration of EBV-harboring lymphocytes occurs in a large subset of bladder cancers cases. It is more frequently associated with advanced stages. EBV infection in tumor cells is very limited. Our findings suggest that EBV-positive lymphocytes might play a role in bladder cancer progression.
authors.affiliation: Department of Urology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. takataka@rf6.so-net.ne.jp
authors.forename: Takashige
authors.initials: T
authors.lastname: Abe
authors.forename: Nobuo
authors.initials: N
authors.lastname: Shinohara
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Tada
authors.forename: Toru
authors.initials: T
authors.lastname: Harabayashi
authors.forename: Ataru
authors.initials: A
authors.lastname: Sazawa
authors.forename: Satoru
authors.initials: S
authors.lastname: Maruyama
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Moriuchi
authors.forename: Kenzo
authors.initials: K
authors.lastname: Takada
authors.forename: Katsuya
authors.initials: K
authors.lastname: Nonomura
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D004854:Herpesvirus 4, Human; D006801:Humans; D007564:Japan; D016246:Lymphocytes, Tumor-Infiltrating / Q000821:virology*; D008297:Male; D008875:Middle Aged; D001749:Urinary Bladder Neoplasms / Q000473:pathology*