Classification of renal cell carcinoma based on expression of VEGF and VEGF receptors in both tumor cells and endothelial cells
Recent development of antiangiogenic therapy for renal cell carcinoma (RCC) has significantly improved the treatment of these often refractory tumors. However, not all patients respond to therapy and assays for predicting outcome are needed. As a first step, we analyzed a retrospective cohort of tum...
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| Veröffentlicht in: | Laboratory investigation 2008-09, Vol.88 (9), p.962-972 |
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| creator | Kluger, Harriet M Siddiqui, Summar F Angeletti, Cesar Sznol, Mario Kelly, William K Molinaro, Annette M Camp, Robert L |
| description | Recent development of antiangiogenic therapy for renal cell carcinoma (RCC) has significantly improved the treatment of these often refractory tumors. However, not all patients respond to therapy and assays for predicting outcome are needed. As a first step, we analyzed a retrospective cohort of tumors and assessed the ability of VEGF and VEGF receptors (VEGF-R1, -R2 and -R3) to classify tumors. We analyzed tissue microarrays containing 330 RCCs using a novel method of automated quantitative analysis of VEGF and VEGF-R expression by fluorescent immunohistochemistry. Expression of markers was separately quantified within three tissue components: tumor cells, endothelial cells and adjacent normal epithelium. VEGF and VEGF receptors were tightly coexpressed both within tumors and within adjacent normal cells (all
P
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| doi_str_mv | 10.1038/labinvest.2008.65 |
| format | Article |
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P
-values <0.001). Tumor cell expression of VEGF-R1 and -R2 was strongly and inversely correlated with vessel area (
P
<0.0001). Unsupervised hierarchical clustering classified tumors by coordinated expression of VEGF and VEGF-Rs. The distribution of clear cell and papillary tumors was not significantly different between clusters. Clusters with high expression of VEGF and VEGF-Rs in the tumor cells exhibited poor survival when compared with the other clusters on uni- and multivariable analysis. VEGF and VEGF receptors exhibit a complex pattern of coordinated expression in RCC. Clustering tumors by VEGF and VEGF-R in tissue components demonstrates distinct tumor phenotypes with different outcomes, and may provide a means for determining which tumors will respond to what antiangiogenic therapies.</description><identifier>ISSN: 0023-6837</identifier><identifier>EISSN: 1530-0307</identifier><identifier>DOI: 10.1038/labinvest.2008.65</identifier><identifier>PMID: 18626467</identifier><identifier>CODEN: LAINAW</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Biological and medical sciences ; Biotechnology ; Carcinoma, Renal Cell - classification ; Carcinoma, Renal Cell - metabolism ; Endothelium, Vascular - metabolism ; Fundamental and applied biological sciences. Psychology ; Humans ; Immunohistochemistry ; Investigative techniques, diagnostic techniques (general aspects) ; Kidney Neoplasms - classification ; Kidney Neoplasms - metabolism ; Laboratory Medicine ; Medical sciences ; Medicine ; Medicine & Public Health ; Middle Aged ; Pathology ; Receptors, Vascular Endothelial Growth Factor - metabolism ; research-article ; Tissue Array Analysis ; Vascular Endothelial Growth Factor A - metabolism</subject><ispartof>Laboratory investigation, 2008-09, Vol.88 (9), p.962-972</ispartof><rights>United States and Canadian Academy of Pathology, Inc. 2008</rights><rights>2008 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Sep 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c429t-52de7754062a0c59bcefc2427b72b0a11bbfd16ac3ea1e31f2406bfc929756ac3</citedby><cites>FETCH-LOGICAL-c429t-52de7754062a0c59bcefc2427b72b0a11bbfd16ac3ea1e31f2406bfc929756ac3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20612508$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18626467$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kluger, Harriet M</creatorcontrib><creatorcontrib>Siddiqui, Summar F</creatorcontrib><creatorcontrib>Angeletti, Cesar</creatorcontrib><creatorcontrib>Sznol, Mario</creatorcontrib><creatorcontrib>Kelly, William K</creatorcontrib><creatorcontrib>Molinaro, Annette M</creatorcontrib><creatorcontrib>Camp, Robert L</creatorcontrib><title>Classification of renal cell carcinoma based on expression of VEGF and VEGF receptors in both tumor cells and endothelial cells</title><title>Laboratory investigation</title><addtitle>Lab Invest</addtitle><addtitle>Lab Invest</addtitle><description>Recent development of antiangiogenic therapy for renal cell carcinoma (RCC) has significantly improved the treatment of these often refractory tumors. However, not all patients respond to therapy and assays for predicting outcome are needed. As a first step, we analyzed a retrospective cohort of tumors and assessed the ability of VEGF and VEGF receptors (VEGF-R1, -R2 and -R3) to classify tumors. We analyzed tissue microarrays containing 330 RCCs using a novel method of automated quantitative analysis of VEGF and VEGF-R expression by fluorescent immunohistochemistry. Expression of markers was separately quantified within three tissue components: tumor cells, endothelial cells and adjacent normal epithelium. VEGF and VEGF receptors were tightly coexpressed both within tumors and within adjacent normal cells (all
P
-values <0.001). Tumor cell expression of VEGF-R1 and -R2 was strongly and inversely correlated with vessel area (
P
<0.0001). Unsupervised hierarchical clustering classified tumors by coordinated expression of VEGF and VEGF-Rs. The distribution of clear cell and papillary tumors was not significantly different between clusters. Clusters with high expression of VEGF and VEGF-Rs in the tumor cells exhibited poor survival when compared with the other clusters on uni- and multivariable analysis. VEGF and VEGF receptors exhibit a complex pattern of coordinated expression in RCC. Clustering tumors by VEGF and VEGF-R in tissue components demonstrates distinct tumor phenotypes with different outcomes, and may provide a means for determining which tumors will respond to what antiangiogenic therapies.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>Carcinoma, Renal Cell - classification</subject><subject>Carcinoma, Renal Cell - metabolism</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Kidney Neoplasms - classification</subject><subject>Kidney Neoplasms - metabolism</subject><subject>Laboratory Medicine</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Pathology</subject><subject>Receptors, Vascular Endothelial Growth Factor - metabolism</subject><subject>research-article</subject><subject>Tissue Array Analysis</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><issn>0023-6837</issn><issn>1530-0307</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</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><recordid>eNp90cFu1DAQBmCrArVL4QG4oAgJbllsJ7aTI1q1BakSl5arNXYm4CqxFztBcOLVcZpoK3HgEkf2N7-tGUJeM7pntGo-DGCc_4lp2nNKm70UZ2THREVLWlH1jOwo5VUpm0pdkBcpPVDK6lqKc3LBGsllLdWO_DkMkJLrnYXJBV-EvojoYSgsDvkD0TofRigMJOyKDPDXMWKuWO3Xq5vrAny3_kS0eJxCTIXzhQnT92KaxxAfs9IjQ9_lbRzcdkN6SZ73MCR8ta2X5P766u7wqbz9cvP58PG2tDVvp1LwDpUSNZUcqBWtsdhbXnNlFDcUGDOm75gEWyEwrFjPMzW9bXmrxLJ9Sd6vuccYfsy5ZXp0aXkBeAxz0rLN7WjbOsO3_8CHMMfckaQ5p1wpVi2IrcjGkFLEXh-jGyH-1ozqZTT6NBq9jEZLkWvebMGzGbF7qthmkcG7DUCyMPQRvHXp5DiVjAvaZMdXl_KR_4bx6YX_u30L9zDNEU-pJ7nA7P4CVkS4wA</recordid><startdate>20080901</startdate><enddate>20080901</enddate><creator>Kluger, Harriet M</creator><creator>Siddiqui, Summar F</creator><creator>Angeletti, Cesar</creator><creator>Sznol, Mario</creator><creator>Kelly, William K</creator><creator>Molinaro, Annette M</creator><creator>Camp, Robert L</creator><general>Nature Publishing Group US</general><general>Nature Publishing</general><general>Nature Publishing Group</general><scope>IQODW</scope><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>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</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>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20080901</creationdate><title>Classification of renal cell carcinoma based on expression of VEGF and VEGF receptors in both tumor cells and endothelial cells</title><author>Kluger, Harriet M ; Siddiqui, Summar F ; Angeletti, Cesar ; Sznol, Mario ; Kelly, William K ; Molinaro, Annette M ; Camp, Robert L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c429t-52de7754062a0c59bcefc2427b72b0a11bbfd16ac3ea1e31f2406bfc929756ac3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biological and medical sciences</topic><topic>Biotechnology</topic><topic>Carcinoma, Renal Cell - classification</topic><topic>Carcinoma, Renal Cell - metabolism</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Kidney Neoplasms - classification</topic><topic>Kidney Neoplasms - metabolism</topic><topic>Laboratory Medicine</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Pathology</topic><topic>Receptors, Vascular Endothelial Growth Factor - metabolism</topic><topic>research-article</topic><topic>Tissue Array Analysis</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kluger, Harriet M</creatorcontrib><creatorcontrib>Siddiqui, Summar F</creatorcontrib><creatorcontrib>Angeletti, Cesar</creatorcontrib><creatorcontrib>Sznol, Mario</creatorcontrib><creatorcontrib>Kelly, William K</creatorcontrib><creatorcontrib>Molinaro, Annette M</creatorcontrib><creatorcontrib>Camp, Robert L</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Laboratory investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kluger, Harriet M</au><au>Siddiqui, Summar F</au><au>Angeletti, Cesar</au><au>Sznol, Mario</au><au>Kelly, William K</au><au>Molinaro, Annette M</au><au>Camp, Robert L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Classification of renal cell carcinoma based on expression of VEGF and VEGF receptors in both tumor cells and endothelial cells</atitle><jtitle>Laboratory investigation</jtitle><stitle>Lab Invest</stitle><addtitle>Lab Invest</addtitle><date>2008-09-01</date><risdate>2008</risdate><volume>88</volume><issue>9</issue><spage>962</spage><epage>972</epage><pages>962-972</pages><issn>0023-6837</issn><eissn>1530-0307</eissn><coden>LAINAW</coden><abstract>Recent development of antiangiogenic therapy for renal cell carcinoma (RCC) has significantly improved the treatment of these often refractory tumors. However, not all patients respond to therapy and assays for predicting outcome are needed. As a first step, we analyzed a retrospective cohort of tumors and assessed the ability of VEGF and VEGF receptors (VEGF-R1, -R2 and -R3) to classify tumors. We analyzed tissue microarrays containing 330 RCCs using a novel method of automated quantitative analysis of VEGF and VEGF-R expression by fluorescent immunohistochemistry. Expression of markers was separately quantified within three tissue components: tumor cells, endothelial cells and adjacent normal epithelium. VEGF and VEGF receptors were tightly coexpressed both within tumors and within adjacent normal cells (all
P
-values <0.001). Tumor cell expression of VEGF-R1 and -R2 was strongly and inversely correlated with vessel area (
P
<0.0001). Unsupervised hierarchical clustering classified tumors by coordinated expression of VEGF and VEGF-Rs. The distribution of clear cell and papillary tumors was not significantly different between clusters. Clusters with high expression of VEGF and VEGF-Rs in the tumor cells exhibited poor survival when compared with the other clusters on uni- and multivariable analysis. VEGF and VEGF receptors exhibit a complex pattern of coordinated expression in RCC. Clustering tumors by VEGF and VEGF-R in tissue components demonstrates distinct tumor phenotypes with different outcomes, and may provide a means for determining which tumors will respond to what antiangiogenic therapies.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>18626467</pmid><doi>10.1038/labinvest.2008.65</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Biological and medical sciences Biotechnology Carcinoma, Renal Cell - classification Carcinoma, Renal Cell - metabolism Endothelium, Vascular - metabolism Fundamental and applied biological sciences. Psychology Humans Immunohistochemistry Investigative techniques, diagnostic techniques (general aspects) Kidney Neoplasms - classification Kidney Neoplasms - metabolism Laboratory Medicine Medical sciences Medicine Medicine & Public Health Middle Aged Pathology Receptors, Vascular Endothelial Growth Factor - metabolism research-article Tissue Array Analysis Vascular Endothelial Growth Factor A - metabolism |
| title | Classification of renal cell carcinoma based on expression of VEGF and VEGF receptors in both tumor cells and endothelial cells |
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