Prognostic value of the expression of Ki‐67, CD44 and vascular endothelial growth factor, and microvessel invasion, in renal cell carcinoma

OBJECTIVE To determine if use of cell proliferation, cell adhesion, level of angiogenesis‐related factors and presence of microscopic vascular invasion (MVI) could better predict the biological behaviour of renal cell carcinoma (RCC), which has a widely variable clinical outcome despite the use of c...

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Veröffentlicht in:BJU international 2004-05, Vol.93 (7), p.1087-1093
Hauptverfasser: Yildiz, E., Gokce, G., Kilicarslan, H., Ayan, S., Goze, O.F., Gultekin, E.Y.
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container_end_page 1093
container_issue 7
container_start_page 1087
container_title BJU international
container_volume 93
creator Yildiz, E.
Gokce, G.
Kilicarslan, H.
Ayan, S.
Goze, O.F.
Gultekin, E.Y.
description OBJECTIVE To determine if use of cell proliferation, cell adhesion, level of angiogenesis‐related factors and presence of microscopic vascular invasion (MVI) could better predict the biological behaviour of renal cell carcinoma (RCC), which has a widely variable clinical outcome despite the use of conventional prognostic factors (staging and grading). MATERIALS AND METHODS The expression of Ki‐67, CD44H and vascular endothelial growth factor (VEGF) were assessed immunohistochemically in formalin‐fixed, paraffin‐embedded tissues from 48 RCCs, using a Ki‐67 labelling index (LI), CD44 LI and level of VEGF expression, respectively. In addition all the pathological slides were reviewed retrospectively for the presence and absence of MVI. The prognostic value of all the variables assessed was then evaluated, and correlated with the usual prognostic variables and cancer‐specific survival. RESULTS Univariate analysis of cancer‐specific survival showed that tumour stage (P 
doi_str_mv 10.1111/j.1464-410X.2004.04786.x
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MATERIALS AND METHODS The expression of Ki‐67, CD44H and vascular endothelial growth factor (VEGF) were assessed immunohistochemically in formalin‐fixed, paraffin‐embedded tissues from 48 RCCs, using a Ki‐67 labelling index (LI), CD44 LI and level of VEGF expression, respectively. In addition all the pathological slides were reviewed retrospectively for the presence and absence of MVI. The prognostic value of all the variables assessed was then evaluated, and correlated with the usual prognostic variables and cancer‐specific survival. RESULTS Univariate analysis of cancer‐specific survival showed that tumour stage (P &lt; 0.001), tumour size (P = 0.005), metastasis, MVI, Ki‐67 LI, CD44H LI and VEGF expression (all P &lt; 0.001) were predictors of tumour‐related death. There was a statistical correlation between CD44H LI and each of Ki‐67 LI (r = 0.61), expression level of VEGF (r = 0.72) and presence of MVI (r = 0.71). Independent predictors of cancer‐specific survival in a multivariate analysis were: in all patients with RCC, the MVI (P = 0.003) and VEGF expression (P = 0.01); in those with no metastases, MVI (P = 0.01); in patients with no MVI, VEGF (P = 0.04); and in patients with MVI, Ki‐67 LI (P = 0.003). No independent predictor was identified in patient with metastases. CONCLUSION This study suggests that cell proliferation, cell adhesion, the level of VEGF expression and the presence of MVI represent a complex tumour‐host interaction that may favour the progression of RCC. Cell proliferation, CD44H and VEGF expression appear to be powerful markers for identifying patients with an adverse prognosis.</description><identifier>ISSN: 1464-4096</identifier><identifier>EISSN: 1464-410X</identifier><identifier>DOI: 10.1111/j.1464-410X.2004.04786.x</identifier><identifier>PMID: 15142169</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Biological and medical sciences ; Carcinoma, Renal Cell - blood supply ; Carcinoma, Renal Cell - metabolism ; CD44 ; Female ; Humans ; Hyaluronan Receptors - metabolism ; Immunohistochemistry ; Ki-67 Antigen - metabolism ; Kidney Neoplasms - blood supply ; Kidney Neoplasms - metabolism ; Kidneys ; Ki‐67 ; Male ; Medical sciences ; Microcirculation ; microvessel invasion ; Middle Aged ; Neoplasm Proteins - metabolism ; Nephrology. Urinary tract diseases ; Prognosis ; renal cell carcinoma ; Survival Analysis ; Tumors of the urinary system ; Vascular Endothelial Growth Factors - metabolism ; VEGF</subject><ispartof>BJU international, 2004-05, Vol.93 (7), p.1087-1093</ispartof><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5116-3f444e6d6c45d7a797aa685f80f526f5a870b2eb15d0728062593db6d5807b583</citedby><cites>FETCH-LOGICAL-c5116-3f444e6d6c45d7a797aa685f80f526f5a870b2eb15d0728062593db6d5807b583</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1464-410X.2004.04786.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1464-410X.2004.04786.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=15768074$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15142169$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yildiz, E.</creatorcontrib><creatorcontrib>Gokce, G.</creatorcontrib><creatorcontrib>Kilicarslan, H.</creatorcontrib><creatorcontrib>Ayan, S.</creatorcontrib><creatorcontrib>Goze, O.F.</creatorcontrib><creatorcontrib>Gultekin, E.Y.</creatorcontrib><title>Prognostic value of the expression of Ki‐67, CD44 and vascular endothelial growth factor, and microvessel invasion, in renal cell carcinoma</title><title>BJU international</title><addtitle>BJU Int</addtitle><description>OBJECTIVE To determine if use of cell proliferation, cell adhesion, level of angiogenesis‐related factors and presence of microscopic vascular invasion (MVI) could better predict the biological behaviour of renal cell carcinoma (RCC), which has a widely variable clinical outcome despite the use of conventional prognostic factors (staging and grading). MATERIALS AND METHODS The expression of Ki‐67, CD44H and vascular endothelial growth factor (VEGF) were assessed immunohistochemically in formalin‐fixed, paraffin‐embedded tissues from 48 RCCs, using a Ki‐67 labelling index (LI), CD44 LI and level of VEGF expression, respectively. In addition all the pathological slides were reviewed retrospectively for the presence and absence of MVI. The prognostic value of all the variables assessed was then evaluated, and correlated with the usual prognostic variables and cancer‐specific survival. RESULTS Univariate analysis of cancer‐specific survival showed that tumour stage (P &lt; 0.001), tumour size (P = 0.005), metastasis, MVI, Ki‐67 LI, CD44H LI and VEGF expression (all P &lt; 0.001) were predictors of tumour‐related death. There was a statistical correlation between CD44H LI and each of Ki‐67 LI (r = 0.61), expression level of VEGF (r = 0.72) and presence of MVI (r = 0.71). Independent predictors of cancer‐specific survival in a multivariate analysis were: in all patients with RCC, the MVI (P = 0.003) and VEGF expression (P = 0.01); in those with no metastases, MVI (P = 0.01); in patients with no MVI, VEGF (P = 0.04); and in patients with MVI, Ki‐67 LI (P = 0.003). No independent predictor was identified in patient with metastases. CONCLUSION This study suggests that cell proliferation, cell adhesion, the level of VEGF expression and the presence of MVI represent a complex tumour‐host interaction that may favour the progression of RCC. Cell proliferation, CD44H and VEGF expression appear to be powerful markers for identifying patients with an adverse prognosis.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Renal Cell - blood supply</subject><subject>Carcinoma, Renal Cell - metabolism</subject><subject>CD44</subject><subject>Female</subject><subject>Humans</subject><subject>Hyaluronan Receptors - metabolism</subject><subject>Immunohistochemistry</subject><subject>Ki-67 Antigen - metabolism</subject><subject>Kidney Neoplasms - blood supply</subject><subject>Kidney Neoplasms - metabolism</subject><subject>Kidneys</subject><subject>Ki‐67</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microcirculation</subject><subject>microvessel invasion</subject><subject>Middle Aged</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Prognosis</subject><subject>renal cell carcinoma</subject><subject>Survival Analysis</subject><subject>Tumors of the urinary system</subject><subject>Vascular Endothelial Growth Factors - metabolism</subject><subject>VEGF</subject><issn>1464-4096</issn><issn>1464-410X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc9O3DAQxi3UCijlFZAv7Wk32In_JIce2m1LaZHaQ5G4WY5jg1eOvdgJLLe-QKU-I09Sh91Cj_hgj8a_bzz-BgCIUYHzOl4WmDAyJxhdFCVCpECE16xY74D9x4sX_2LUsD3wKqUlQjnB6C7YwxSTErNmH_z-EcOlD2mwCt5IN2oYDByuNNTrVdQp2eCnzDd7_-sP4zO4-EgIlL7LcFKjkxFq34UscFY6eBnD7XAFjVRDiLMHrrcqhptcSTtofVblirMcwah9Vijt8iajsj708jV4aaRL-nB7HoDzz59-Lr7Mz76fnC7en80VxZjNK0MI0axjitCOS95wKVlNTY0MLZmhsuaoLXWLaYd4WSNW0qbqWtbRGvGW1tUBeLupu4rhetRpEL1NUyvS6zAmwXFT0grxDNYbMH8ipaiNWEXby3gnMBLTKMRSTC6LyXExjUI8jEKss_Ro-8bY9rp7Em69z8CbLZCtlM5E6ZVN_3Gc5XZJ5t5tuFvr9N2zGxAfvp5PUfUXfEamLA</recordid><startdate>200405</startdate><enddate>200405</enddate><creator>Yildiz, E.</creator><creator>Gokce, G.</creator><creator>Kilicarslan, H.</creator><creator>Ayan, S.</creator><creator>Goze, O.F.</creator><creator>Gultekin, E.Y.</creator><general>Blackwell Science Ltd</general><general>Blackwell</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>7X8</scope></search><sort><creationdate>200405</creationdate><title>Prognostic value of the expression of Ki‐67, CD44 and vascular endothelial growth factor, and microvessel invasion, in renal cell carcinoma</title><author>Yildiz, E. ; Gokce, G. ; Kilicarslan, H. ; Ayan, S. ; Goze, O.F. ; Gultekin, E.Y.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5116-3f444e6d6c45d7a797aa685f80f526f5a870b2eb15d0728062593db6d5807b583</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Renal Cell - blood supply</topic><topic>Carcinoma, Renal Cell - metabolism</topic><topic>CD44</topic><topic>Female</topic><topic>Humans</topic><topic>Hyaluronan Receptors - metabolism</topic><topic>Immunohistochemistry</topic><topic>Ki-67 Antigen - metabolism</topic><topic>Kidney Neoplasms - blood supply</topic><topic>Kidney Neoplasms - metabolism</topic><topic>Kidneys</topic><topic>Ki‐67</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microcirculation</topic><topic>microvessel invasion</topic><topic>Middle Aged</topic><topic>Neoplasm Proteins - metabolism</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Prognosis</topic><topic>renal cell carcinoma</topic><topic>Survival Analysis</topic><topic>Tumors of the urinary system</topic><topic>Vascular Endothelial Growth Factors - metabolism</topic><topic>VEGF</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yildiz, E.</creatorcontrib><creatorcontrib>Gokce, G.</creatorcontrib><creatorcontrib>Kilicarslan, H.</creatorcontrib><creatorcontrib>Ayan, S.</creatorcontrib><creatorcontrib>Goze, O.F.</creatorcontrib><creatorcontrib>Gultekin, E.Y.</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>MEDLINE - Academic</collection><jtitle>BJU international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yildiz, E.</au><au>Gokce, G.</au><au>Kilicarslan, H.</au><au>Ayan, S.</au><au>Goze, O.F.</au><au>Gultekin, E.Y.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prognostic value of the expression of Ki‐67, CD44 and vascular endothelial growth factor, and microvessel invasion, in renal cell carcinoma</atitle><jtitle>BJU international</jtitle><addtitle>BJU Int</addtitle><date>2004-05</date><risdate>2004</risdate><volume>93</volume><issue>7</issue><spage>1087</spage><epage>1093</epage><pages>1087-1093</pages><issn>1464-4096</issn><eissn>1464-410X</eissn><abstract>OBJECTIVE To determine if use of cell proliferation, cell adhesion, level of angiogenesis‐related factors and presence of microscopic vascular invasion (MVI) could better predict the biological behaviour of renal cell carcinoma (RCC), which has a widely variable clinical outcome despite the use of conventional prognostic factors (staging and grading). MATERIALS AND METHODS The expression of Ki‐67, CD44H and vascular endothelial growth factor (VEGF) were assessed immunohistochemically in formalin‐fixed, paraffin‐embedded tissues from 48 RCCs, using a Ki‐67 labelling index (LI), CD44 LI and level of VEGF expression, respectively. In addition all the pathological slides were reviewed retrospectively for the presence and absence of MVI. The prognostic value of all the variables assessed was then evaluated, and correlated with the usual prognostic variables and cancer‐specific survival. RESULTS Univariate analysis of cancer‐specific survival showed that tumour stage (P &lt; 0.001), tumour size (P = 0.005), metastasis, MVI, Ki‐67 LI, CD44H LI and VEGF expression (all P &lt; 0.001) were predictors of tumour‐related death. There was a statistical correlation between CD44H LI and each of Ki‐67 LI (r = 0.61), expression level of VEGF (r = 0.72) and presence of MVI (r = 0.71). Independent predictors of cancer‐specific survival in a multivariate analysis were: in all patients with RCC, the MVI (P = 0.003) and VEGF expression (P = 0.01); in those with no metastases, MVI (P = 0.01); in patients with no MVI, VEGF (P = 0.04); and in patients with MVI, Ki‐67 LI (P = 0.003). No independent predictor was identified in patient with metastases. CONCLUSION This study suggests that cell proliferation, cell adhesion, the level of VEGF expression and the presence of MVI represent a complex tumour‐host interaction that may favour the progression of RCC. Cell proliferation, CD44H and VEGF expression appear to be powerful markers for identifying patients with an adverse prognosis.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>15142169</pmid><doi>10.1111/j.1464-410X.2004.04786.x</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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source Wiley Online Library - AutoHoldings Journals; MEDLINE
subjects Adult
Aged
Aged, 80 and over
Biological and medical sciences
Carcinoma, Renal Cell - blood supply
Carcinoma, Renal Cell - metabolism
CD44
Female
Humans
Hyaluronan Receptors - metabolism
Immunohistochemistry
Ki-67 Antigen - metabolism
Kidney Neoplasms - blood supply
Kidney Neoplasms - metabolism
Kidneys
Ki‐67
Male
Medical sciences
Microcirculation
microvessel invasion
Middle Aged
Neoplasm Proteins - metabolism
Nephrology. Urinary tract diseases
Prognosis
renal cell carcinoma
Survival Analysis
Tumors of the urinary system
Vascular Endothelial Growth Factors - metabolism
VEGF
title Prognostic value of the expression of Ki‐67, CD44 and vascular endothelial growth factor, and microvessel invasion, in renal cell carcinoma
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