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 dur...
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| creator | 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 |
| description | 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. |
| doi_str_mv | 10.1371/journal.pone.0135824 |
| format | Article |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0135824</identifier><identifier>PMID: 26292086</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Aged ; Antigens ; Biomarkers, Tumor - analysis ; Bladder ; Bladder cancer ; Cancer ; Chemotherapy ; Cloning ; Extracellular matrix ; Female ; Gene expression ; Health risks ; Humans ; Immunoglobulins ; Immunohistochemistry ; Invasiveness ; Laboratories ; Lung cancer ; Macrophages ; Male ; Medical prognosis ; Metastases ; Metastasis ; Middle Aged ; Molecular chains ; Oncology ; Paraffin ; Pathology ; Patients ; Position (location) ; Prostate ; Receptors, Urokinase Plasminogen Activator - analysis ; Receptors, Urokinase Plasminogen Activator - metabolism ; Retrospective Studies ; Survival ; Tumors ; U-Plasminogen activator ; Urinary Bladder - chemistry ; Urinary Bladder - pathology ; Urinary Bladder Neoplasms - chemistry ; Urinary Bladder Neoplasms - metabolism ; Urinary Bladder Neoplasms - pathology ; Urokinase ; Urology ; Urothelial carcinoma ; Urothelium - chemistry ; Urothelium - metabolism ; Urothelium - pathology</subject><ispartof>PloS one, 2015-08, Vol.10 (8), p.e0135824-e0135824</ispartof><rights>2015 Dohn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Dohn et al 2015 Dohn et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-6ecc9530ca0a28888afe1daeafd9fa468b37868c6378a8f9129a95fb8563a7033</citedby><cites>FETCH-LOGICAL-c526t-6ecc9530ca0a28888afe1daeafd9fa468b37868c6378a8f9129a95fb8563a7033</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546385/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546385/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26292086$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Ahmad, Aamir</contributor><creatorcontrib>Dohn, Line Hammer</creatorcontrib><creatorcontrib>Pappot, Helle</creatorcontrib><creatorcontrib>Iversen, Benedikte Richter</creatorcontrib><creatorcontrib>Illemann, Martin</creatorcontrib><creatorcontrib>Høyer-Hansen, Gunilla</creatorcontrib><creatorcontrib>Christensen, Ib Jarle</creatorcontrib><creatorcontrib>Thind, Peter</creatorcontrib><creatorcontrib>Salling, Lisbeth</creatorcontrib><creatorcontrib>von der Maase, Hans</creatorcontrib><creatorcontrib>Laerum, Ole Didrik</creatorcontrib><title>uPAR Expression Pattern in Patients with Urothelial Carcinoma of the Bladder--Possible Clinical Implications</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.</description><subject>Adult</subject><subject>Aged</subject><subject>Antigens</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Bladder</subject><subject>Bladder cancer</subject><subject>Cancer</subject><subject>Chemotherapy</subject><subject>Cloning</subject><subject>Extracellular matrix</subject><subject>Female</subject><subject>Gene expression</subject><subject>Health risks</subject><subject>Humans</subject><subject>Immunoglobulins</subject><subject>Immunohistochemistry</subject><subject>Invasiveness</subject><subject>Laboratories</subject><subject>Lung cancer</subject><subject>Macrophages</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Molecular chains</subject><subject>Oncology</subject><subject>Paraffin</subject><subject>Pathology</subject><subject>Patients</subject><subject>Position (location)</subject><subject>Prostate</subject><subject>Receptors, Urokinase Plasminogen Activator - analysis</subject><subject>Receptors, Urokinase Plasminogen Activator - metabolism</subject><subject>Retrospective Studies</subject><subject>Survival</subject><subject>Tumors</subject><subject>U-Plasminogen activator</subject><subject>Urinary Bladder - chemistry</subject><subject>Urinary Bladder - pathology</subject><subject>Urinary Bladder Neoplasms - chemistry</subject><subject>Urinary Bladder Neoplasms - metabolism</subject><subject>Urinary Bladder Neoplasms - pathology</subject><subject>Urokinase</subject><subject>Urology</subject><subject>Urothelial carcinoma</subject><subject>Urothelium - chemistry</subject><subject>Urothelium - metabolism</subject><subject>Urothelium - pathology</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNptUk1v1DAQjRAVLYV_gMASFy5Z_BE7zgWprApdqRIrRM_WxLG7XjnxYicF_j3e3bRqEb7MaPzmzdcrijcELwirycdtmOIAfrELg1lgwrik1bPijDSMloJi9vyRf1q8TGmLMWdSiBfFKRW0oViKs8JP64vv6PL3LpqUXBjQGsbRxAG5g-vMMCb0y40bdBPDuDHegUdLiNoNoQcULMpB9NlD15lYluuQWVpv0NK7wemMXfU7n50xc6dXxYkFn8zr2Z4XN18ufyyvyutvX1fLi-tScyrGUhitG86wBgxU5gfWkA4M2K6xUAnZsloKqUU2IG1DaAMNt63kgkGNGTsv3h15dz4kNS8qKVJjWUkqqz1idUR0AbZqF10P8Y8K4NQhEOKtgjg67Y1qaEOEJNTyVlY1E9ISmhuqjeRdg2uSuT7N1aa2N53OK4vgn5A-_RncRt2GO1XxSjDJM8GHmSCGn5NJo-pd0sZ7GEyYDn3nI-aF7KHv_4H-f7rqiNIx3yMa-9AMwWovnvsstRePmsWT094-HuQh6V4t7C9Tv8MC</recordid><startdate>20150820</startdate><enddate>20150820</enddate><creator>Dohn, Line Hammer</creator><creator>Pappot, Helle</creator><creator>Iversen, Benedikte Richter</creator><creator>Illemann, Martin</creator><creator>Høyer-Hansen, Gunilla</creator><creator>Christensen, Ib Jarle</creator><creator>Thind, Peter</creator><creator>Salling, Lisbeth</creator><creator>von der Maase, Hans</creator><creator>Laerum, Ole Didrik</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150820</creationdate><title>uPAR Expression Pattern in Patients with Urothelial Carcinoma of the Bladder--Possible Clinical Implications</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-6ecc9530ca0a28888afe1daeafd9fa468b37868c6378a8f9129a95fb8563a7033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antigens</topic><topic>Biomarkers, Tumor - analysis</topic><topic>Bladder</topic><topic>Bladder cancer</topic><topic>Cancer</topic><topic>Chemotherapy</topic><topic>Cloning</topic><topic>Extracellular matrix</topic><topic>Female</topic><topic>Gene expression</topic><topic>Health risks</topic><topic>Humans</topic><topic>Immunoglobulins</topic><topic>Immunohistochemistry</topic><topic>Invasiveness</topic><topic>Laboratories</topic><topic>Lung cancer</topic><topic>Macrophages</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Molecular chains</topic><topic>Oncology</topic><topic>Paraffin</topic><topic>Pathology</topic><topic>Patients</topic><topic>Position (location)</topic><topic>Prostate</topic><topic>Receptors, Urokinase Plasminogen Activator - analysis</topic><topic>Receptors, Urokinase Plasminogen Activator - metabolism</topic><topic>Retrospective Studies</topic><topic>Survival</topic><topic>Tumors</topic><topic>U-Plasminogen activator</topic><topic>Urinary Bladder - 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26292086</pmid><doi>10.1371/journal.pone.0135824</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-08, Vol.10 (8), p.e0135824-e0135824 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1708482843 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adult Aged Antigens Biomarkers, Tumor - analysis Bladder Bladder cancer Cancer Chemotherapy Cloning Extracellular matrix Female Gene expression Health risks Humans Immunoglobulins Immunohistochemistry Invasiveness Laboratories Lung cancer Macrophages Male Medical prognosis Metastases Metastasis Middle Aged Molecular chains Oncology Paraffin Pathology Patients Position (location) Prostate Receptors, Urokinase Plasminogen Activator - analysis Receptors, Urokinase Plasminogen Activator - metabolism Retrospective Studies Survival Tumors U-Plasminogen activator Urinary Bladder - chemistry Urinary Bladder - pathology Urinary Bladder Neoplasms - chemistry Urinary Bladder Neoplasms - metabolism Urinary Bladder Neoplasms - pathology Urokinase Urology Urothelial carcinoma Urothelium - chemistry Urothelium - metabolism Urothelium - pathology |
| title | uPAR Expression Pattern in Patients with Urothelial Carcinoma of the Bladder--Possible Clinical Implications |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T08%3A49%3A17IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=uPAR%20Expression%20Pattern%20in%20Patients%20with%20Urothelial%20Carcinoma%20of%20the%20Bladder--Possible%20Clinical%20Implications&rft.jtitle=PloS%20one&rft.au=Dohn,%20Line%20Hammer&rft.date=2015-08-20&rft.volume=10&rft.issue=8&rft.spage=e0135824&rft.epage=e0135824&rft.pages=e0135824-e0135824&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0135824&rft_dat=%3Cproquest_plos_%3E1706205305%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1708482843&rft_id=info:pmid/26292086&rft_doaj_id=oai_doaj_org_article_92916812f5b847368f12afe7e85d9071&rfr_iscdi=true |