uPAR Expression Pattern in Patients with Urothelial Carcinoma of the Bladder--Possible Clinical Implications.

Abstract

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.

• Authors: Line Hammer Dohn, Helle Pappot, Benedikte Richter Iversen, Martin Illemann, Gunilla Høyer-Hansen, Ib Jarle Christensen, Peter Thind, Lisbeth Salling, Hans von der Maase, Ole Didrik Laerum
• Journal: PloS one (PLoS One) Vol. 10 Issue 8 Pg. e0135824 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26292086 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Receptors, Urokinase Plasminogen Activator

Topics

• Adult
• Aged
• Biomarkers, Tumor (analysis)
• Female
• Humans
• Male
• Middle Aged
• Receptors, Urokinase Plasminogen Activator (analysis, metabolism)
• Retrospective Studies
• Urinary Bladder (chemistry, pathology)
• Urinary Bladder Neoplasms (chemistry, metabolism, pathology)
• Urothelium (chemistry, metabolism, pathology)