uPAR Expression Pattern in Patients with Urothelial Carcinoma of the Bladder: Possible Clinical Implications
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uPAR Expression Pattern in Patients with Urothelial Carcinoma of the Bladder : Possible Clinical Implications. / Dohn, Line Hammer; Pappot, Helle; Iversen, Benedikte Richter; Illemann, Martin; Høyer-Hansen, Gunilla; Christensen, Ib Jarle; Thind, Peter; Salling, Lisbeth; von der Maase, Hans; Laerum, Ole Didrik.
In: P L o S One, Vol. 10, No. 8, e0135824, 2015, p. 1-15.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - uPAR Expression Pattern in Patients with Urothelial Carcinoma of the Bladder
T2 - Possible Clinical Implications
AU - Dohn, Line Hammer
AU - Pappot, Helle
AU - Iversen, Benedikte Richter
AU - Illemann, Martin
AU - Høyer-Hansen, Gunilla
AU - Christensen, Ib Jarle
AU - Thind, Peter
AU - Salling, Lisbeth
AU - von der Maase, Hans
AU - Laerum, Ole Didrik
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Biomarkers, Tumor
KW - Female
KW - Humans
KW - Male
KW - Middle Aged
KW - Receptors, Urokinase Plasminogen Activator
KW - Retrospective Studies
KW - Urinary Bladder
KW - Urinary Bladder Neoplasms
KW - Urothelium
U2 - 10.1371/journal.pone.0135824
DO - 10.1371/journal.pone.0135824
M3 - Journal article
C2 - 26292086
VL - 10
SP - 1
EP - 15
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 8
M1 - e0135824
ER -
ID: 162990907