title: The association between the recurrence of solitary non-muscle invasive bladder cancer and tumor infiltrating lymphocytes.
abstract: OBJECTIVE
  To evaluate whether tumor infiltrating lymphocytes (TIL) in biopsy specimens are associated with the clinical outcome of non-muscle invasive bladder cancer.
  
  
  METHODS
  We retrieved tumor specimens from 115 patients with solitary papillary non-muscle invasive bladder cancer treated between 1996 and 2006 and constructed tissue microarrays. Patients were divided in two groups: those with recurrent disease (N=69) and those without recurrent disease (N=46) during the follow up of minimum 5 years. All patients were treated with initial transurethral resection and none received adjuvant therapy. Immunhistochemical staining was performed with anti-CD3, CD4, CD8, and Granzyme B (GrB). The CD4+:CD8+ and GrB+:CD8 ratios were determined.
  
  
  RESULTS
  Tumor infiltrating lymphocytes were predominantly observed within cancer stroma, and only rare individual cells were observed intraepithelially. The group without recurrent disease had lower levels of CD3+ and CD8+ lymphocytes than the group with recurrent disease (P=0.0001, P=0.0002, respectively). The CD4+:GrB+ and GrB+:CD8+ ratios were significantly higher in patients without recurrent disease (P=0.0002, P=0.039, respectively).
  
  
  CONCLUSIONS
  This study revealed a possible connection between TIL number and bladder cancer recurrence. TIL subset ratio showed different patterns in recurrent and non-recurrent tumors, which is why it could become a useful a prognostic clinical index if our findings are confirmed in randomized trials.
authors.affiliation: Department of Urology, Clinical Hospital Center Rijeka, Tome Strizica 3, 51000 Rijeka, Croatia. rpinak@gmail.com
authors.forename: Kristian
authors.initials: K
authors.lastname: Krpina
authors.forename: Emina
authors.initials: E
authors.lastname: Babarović
authors.forename: Gordana
authors.initials: G
authors.lastname: Dorđević
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Fuckar
authors.forename: Nives
authors.initials: N
authors.lastname: Jonjić
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017252:CD3 Complex / Q000378:metabolism; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D002291:Carcinoma, Papillary / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis*; D011379:Prognosis; D046888:Tissue Array Analysis; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery
chemical_list: D017252:CD3 Complex