uPAR Expression Pattern in Patients with Urothelial Carcinoma of the Bladder--Possible Clinical Implications.
The objective of the present study was to confirm the expression and localisation pattern of the urokinase-type plasminogen activator receptor (uPAR) focusing on its possible clinical relevance in patients with urothelial neoplasia of the bladder. uPAR is a central molecule in tissue remodelling during cancer invasion and metastasis and is an established prognostic marker in various cancer diseases other than bladder cancer. Formalin-fixed and paraffin-embedded tumour-tissue blocks from 186 patients treated with radical cystectomy were analysed. uPAR expression was scored as either negative or positive as well as by the actual score. Separate scores were obtained for cancer cells, macrophages and myofibroblasts at the invasive front and in tumour core. We were able to confirm, in an independent patient cohort, the tissue expression and localisation pattern of uPAR as investigated by Immunohistochemistry as well as a significant association between uPAR positivity and increasing tumour stage and tumour grade. This demonstrates the robustness of our previous and current findings. In addition the association between uPAR positive myofibroblasts and poor survival was reproduced. The highest hazard ratios for survival were seen for uPAR positive myofibroblasts both at the invasive front and in tumour core. Evaluating uPAR expression by the actual score showed a significant association between uPAR positive myofibroblasts in tumour core and an increased risk of cancer specific mortality. Our investigations have generated new and valuable biological information about the cell types being involved in tumour invasion and progression through the plasminogen activation system.
Department of Oncology, Rigshospitalet, Copenhagen, Denmark; The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark.
Line Hammer
LH
Dohn
Department of Oncology, Rigshospitalet, Copenhagen, Denmark.
Helle
H
Pappot
Department of Pathology, Rigshospitalet, Copenhagen, Denmark.
Benedikte Richter
BR
Iversen
The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
Martin
M
Illemann
The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
Gunilla
G
Høyer-Hansen
The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
Ib Jarle
IJ
Christensen
Department of Urology, Rigshospitalet, Copenhagen, Denmark.
Peter
P
Thind
Department of Urology, Rigshospitalet, Copenhagen, Denmark.
Lisbeth
L
Salling
Department of Oncology, Rigshospitalet, Copenhagen, Denmark.
Hans
H
von der Maase
The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
Ole Didrik
OD
Laerum
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D055293:Receptors, Urokinase Plasminogen Activator / Q000032:analysis / Q000378:metabolism*; D012189:Retrospective Studies; D001743:Urinary Bladder / Q000737:chemistry / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D019459:Urothelium / Q000737:chemistry / Q000378:metabolism / Q000473:pathology
D014408:Biomarkers, Tumor; D055293:Receptors, Urokinase Plasminogen Activator