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

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

doi:10.1371/journal.pone.0135824

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

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

9 Citations (Scopus)

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.

Original language	English
Article number	e0135824
Journal	P L o S One
Volume	10
Issue number	8
Pages (from-to)	1-15
Number of pages	15
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0135824
Publication status	Published - 20 Aug 2015

Keywords

Adult
Aged
Biomarkers, Tumor
Female
Humans
Male
Middle Aged
Receptors, Urokinase Plasminogen Activator
Retrospective Studies
Urinary Bladder
Urinary Bladder Neoplasms
Urothelium

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1371/journal.pone.0135824

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@article{d59e7f2cfb3b4a85a146be9d4426b61c,

title = "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.",

keywords = "Adult, Aged, Biomarkers, Tumor, Female, Humans, Male, Middle Aged, Receptors, Urokinase Plasminogen Activator, Retrospective Studies, Urinary Bladder, Urinary Bladder Neoplasms, Urothelium",

author = "Dohn, {Line Hammer} and Helle Pappot and Iversen, {Benedikte Richter} and Martin Illemann and Gunilla H{\o}yer-Hansen and Christensen, {Ib Jarle} and Peter Thind and Lisbeth Salling and {von der Maase}, Hans and Laerum, {Ole Didrik}",

year = "2015",

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doi = "10.1371/journal.pone.0135824",

language = "English",

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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 - 2015/8/20

Y1 - 2015/8/20

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

SN - 1932-6203

VL - 10

SP - 1

EP - 15

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 8

M1 - e0135824

ER -

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

Abstract

Keywords

UN SDGs

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