title: Urokinase-type plasminogen activator receptor (uPAR) expression is associated with T-stage and survival in urothelial carcinoma of the bladder.
abstract: OBJECTIVE
  To evaluate the expression-and localization pattern of the urokinase-type plasminogen activator receptor (uPAR), focusing on its clinical implications in patients with urothelial neoplasia of the bladder treated with radical cystectomy. uPAR is a central molecule in tissue remodeling during cancer invasion and metastasis and is an established prognostic marker in cancer. The expression and localization of uPAR and its prognostic significance is only limitedly investigated in urothelial bladder neoplasia.
  
  
  METHODS
  The expression-and localization pattern of uPAR was investigated in formalin-fixed paraffin-embedded tumor tissue from 149 patients treated with radical cystectomy between 1988 and 2005. uPAR expression was determined by immunohistochemistry and scored as either negative or positive. Separate values were obtained for cancer cells, macrophages, and myofibroblasts at the invasive front and tumor core, respectively. Statistical analyses were performed to evaluate the association of uPAR localization and score with clinicopathologic covariates and survival.
  
  
  RESULTS
  uPAR positivity was seen in 122/137 (89%) and 118/149 (74%) of the neoplasias at the invasive front and tumor core, respectively. uPAR was primarily expressed by myofibroblasts and macrophages in the surrounding stroma as well as some cancer cells. A significant association between uPAR positivity and T-stage as well as grade was found for all 3 cell types in tumor core (P ≤ 0.04 for all comparisons). In univariate analysis, the uPAR positive group had a shorter survival than the uPAR negative group (hazard ratio = 2.39; 95% CI: 1.15-5.01; P = 0.020).
  
  
  CONCLUSIONS
  The expression of uPAR is a possible prognostic marker that could be useful in identification of patients with aggressive, highly invasive tumors that could benefit from additional chemotherapy or more intensive follow-up after cystectomy.
authors.affiliation: Department of Oncology, Rigshospitalet, Copenhagen, Denmark; The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark. Electronic address: line.hammer.dohn@regionh.dk.
authors.forename: Line Hammer
authors.initials: LH
authors.lastname: Dohn
authors.affiliation: The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
authors.forename: Martin
authors.initials: M
authors.lastname: Illemann
authors.affiliation: The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
authors.forename: Gunilla
authors.initials: G
authors.lastname: Høyer-Hansen
authors.affiliation: The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ib J
authors.initials: IJ
authors.lastname: Christensen
authors.affiliation: Department of Clinical Medicine, Section of Urology, University of Bergen, Bergen, Norway.
authors.forename: Jens
authors.initials: J
authors.lastname: Hostmark
authors.affiliation: Department of Clinical Medicine, The Gade Laboratory of Pathology, University of Bergen and Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Jorunn
authors.initials: J
authors.lastname: Litlekalsoy
authors.affiliation: Department of Oncology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Hans
authors.initials: H
authors.lastname: von der Maase
authors.affiliation: Department of Oncology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Helle
authors.initials: H
authors.lastname: Pappot
authors.affiliation: The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, The Gade Laboratory of Pathology, University of Bergen and Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Ole D
authors.initials: OD
authors.lastname: Laerum
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D055293:Receptors, Urokinase Plasminogen Activator / Q000032:analysis / Q000096:biosynthesis*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D055293:Receptors, Urokinase Plasminogen Activator
keywords: Bladder cancer; Invasion; Prognosis; Urothelium; uPAR