WNT5A Expression Increases during Melanoma Progression and Correlates with Outcome

Purpose: Wnt ligands play a major role in development and are important in cancer. Expression microarray analysis correlates one member of this family, WNT5A, to a subclass of melanomas with increased motility and invasion. There are no large studies of clinical samples primarily addressing the impo...

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Veröffentlicht in:Clinical cancer research 2008-09, Vol.14 (18), p.5825-5832
Hauptverfasser: DA FORNO, Philip D, PRINGLE, J. Howard, HUTCHINSON, Peter, OSBORN, Joy, QIANG HUANG, POTTER, Linda, HANCOX, Rachael A, FLETCHER, Alan, SALDANHA, Gerald S
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container_end_page 5832
container_issue 18
container_start_page 5825
container_title Clinical cancer research
container_volume 14
creator DA FORNO, Philip D
PRINGLE, J. Howard
HUTCHINSON, Peter
OSBORN, Joy
QIANG HUANG
POTTER, Linda
HANCOX, Rachael A
FLETCHER, Alan
SALDANHA, Gerald S
description Purpose: Wnt ligands play a major role in development and are important in cancer. Expression microarray analysis correlates one member of this family, WNT5A, to a subclass of melanomas with increased motility and invasion. There are no large studies of clinical samples primarily addressing the importance of WNT5A in melanoma progression or outcome. Therefore, this study aimed to assess the protein expression of WNT5A during melanoma progression and its effect on outcome. Experimental Design: Expression of WNT5A was determined in a series of 59 primary melanomas with matched metastases. To provide a benchmark of progression against which to assess WNT5A, expression of p16 ink4a was analyzed, as this has been previously well documented in melanoma. The effect of WNT5A protein expression on outcome was assessed in 102 melanomas. Results: Cytoplasmic WNT5A showed a trend of increasing expression with melanoma progression ( P = 0.013), whereas there was diminishing p16 ink4a expression ( P = 0.006). Nevi showed relatively strong WNT5A expression. Strong cytoplasmic WNT5A was an independent risk factor for reduced metastasis-free and overall survival in multivariate analysis ( P = 0.001 and 0.003, respectively). Conclusion: Cytoplasmic WNT5A increases with melanoma progression and strong expression is associated with poor outcome.
doi_str_mv 10.1158/1078-0432.CCR-07-5104
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Howard ; HUTCHINSON, Peter ; OSBORN, Joy ; QIANG HUANG ; POTTER, Linda ; HANCOX, Rachael A ; FLETCHER, Alan ; SALDANHA, Gerald S</creator><creatorcontrib>DA FORNO, Philip D ; PRINGLE, J. Howard ; HUTCHINSON, Peter ; OSBORN, Joy ; QIANG HUANG ; POTTER, Linda ; HANCOX, Rachael A ; FLETCHER, Alan ; SALDANHA, Gerald S</creatorcontrib><description>Purpose: Wnt ligands play a major role in development and are important in cancer. Expression microarray analysis correlates one member of this family, WNT5A, to a subclass of melanomas with increased motility and invasion. There are no large studies of clinical samples primarily addressing the importance of WNT5A in melanoma progression or outcome. Therefore, this study aimed to assess the protein expression of WNT5A during melanoma progression and its effect on outcome. Experimental Design: Expression of WNT5A was determined in a series of 59 primary melanomas with matched metastases. To provide a benchmark of progression against which to assess WNT5A, expression of p16 ink4a was analyzed, as this has been previously well documented in melanoma. The effect of WNT5A protein expression on outcome was assessed in 102 melanomas. Results: Cytoplasmic WNT5A showed a trend of increasing expression with melanoma progression ( P = 0.013), whereas there was diminishing p16 ink4a expression ( P = 0.006). Nevi showed relatively strong WNT5A expression. Strong cytoplasmic WNT5A was an independent risk factor for reduced metastasis-free and overall survival in multivariate analysis ( P = 0.001 and 0.003, respectively). Conclusion: Cytoplasmic WNT5A increases with melanoma progression and strong expression is associated with poor outcome.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-07-5104</identifier><identifier>PMID: 18794093</identifier><identifier>CODEN: CCREF4</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Antineoplastic agents ; Biological and medical sciences ; Cell Line, Tumor ; Cyclin-Dependent Kinase Inhibitor p16 - metabolism ; Cytoplasm - metabolism ; Dermatology ; Disease Progression ; Female ; Humans ; Male ; Medical sciences ; melanoma ; Melanoma - metabolism ; Melanoma - pathology ; metastasis ; Middle Aged ; Neoplasm Metastasis ; Pharmacology. Drug treatments ; Prognosis ; progression ; Proto-Oncogene Proteins - metabolism ; Skin Neoplasms - metabolism ; Skin Neoplasms - pathology ; survival ; Survival Analysis ; Tumors of the skin and soft tissue. Premalignant lesions ; Wnt Proteins - metabolism ; Wnt-5a Protein ; WNT5A</subject><ispartof>Clinical cancer research, 2008-09, Vol.14 (18), p.5825-5832</ispartof><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c371t-dec796ede4c7b9b38e3aa73450b34bcd4c5aea4dc67fe965582b05a29c7a11bc3</citedby><cites>FETCH-LOGICAL-c371t-dec796ede4c7b9b38e3aa73450b34bcd4c5aea4dc67fe965582b05a29c7a11bc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3343,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=20992114$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18794093$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>DA FORNO, Philip D</creatorcontrib><creatorcontrib>PRINGLE, J. Howard</creatorcontrib><creatorcontrib>HUTCHINSON, Peter</creatorcontrib><creatorcontrib>OSBORN, Joy</creatorcontrib><creatorcontrib>QIANG HUANG</creatorcontrib><creatorcontrib>POTTER, Linda</creatorcontrib><creatorcontrib>HANCOX, Rachael A</creatorcontrib><creatorcontrib>FLETCHER, Alan</creatorcontrib><creatorcontrib>SALDANHA, Gerald S</creatorcontrib><title>WNT5A Expression Increases during Melanoma Progression and Correlates with Outcome</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Purpose: Wnt ligands play a major role in development and are important in cancer. Expression microarray analysis correlates one member of this family, WNT5A, to a subclass of melanomas with increased motility and invasion. There are no large studies of clinical samples primarily addressing the importance of WNT5A in melanoma progression or outcome. Therefore, this study aimed to assess the protein expression of WNT5A during melanoma progression and its effect on outcome. Experimental Design: Expression of WNT5A was determined in a series of 59 primary melanomas with matched metastases. To provide a benchmark of progression against which to assess WNT5A, expression of p16 ink4a was analyzed, as this has been previously well documented in melanoma. The effect of WNT5A protein expression on outcome was assessed in 102 melanomas. Results: Cytoplasmic WNT5A showed a trend of increasing expression with melanoma progression ( P = 0.013), whereas there was diminishing p16 ink4a expression ( P = 0.006). Nevi showed relatively strong WNT5A expression. Strong cytoplasmic WNT5A was an independent risk factor for reduced metastasis-free and overall survival in multivariate analysis ( P = 0.001 and 0.003, respectively). 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Drug treatments</subject><subject>Prognosis</subject><subject>progression</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Skin Neoplasms - metabolism</subject><subject>Skin Neoplasms - pathology</subject><subject>survival</subject><subject>Survival Analysis</subject><subject>Tumors of the skin and soft tissue. 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Howard ; HUTCHINSON, Peter ; OSBORN, Joy ; QIANG HUANG ; POTTER, Linda ; HANCOX, Rachael A ; FLETCHER, Alan ; SALDANHA, Gerald S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c371t-dec796ede4c7b9b38e3aa73450b34bcd4c5aea4dc67fe965582b05a29c7a11bc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Cell Line, Tumor</topic><topic>Cyclin-Dependent Kinase Inhibitor p16 - metabolism</topic><topic>Cytoplasm - metabolism</topic><topic>Dermatology</topic><topic>Disease Progression</topic><topic>Female</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>melanoma</topic><topic>Melanoma - metabolism</topic><topic>Melanoma - pathology</topic><topic>metastasis</topic><topic>Middle Aged</topic><topic>Neoplasm Metastasis</topic><topic>Pharmacology. Drug treatments</topic><topic>Prognosis</topic><topic>progression</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>Skin Neoplasms - metabolism</topic><topic>Skin Neoplasms - pathology</topic><topic>survival</topic><topic>Survival Analysis</topic><topic>Tumors of the skin and soft tissue. Premalignant lesions</topic><topic>Wnt Proteins - metabolism</topic><topic>Wnt-5a Protein</topic><topic>WNT5A</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>DA FORNO, Philip D</creatorcontrib><creatorcontrib>PRINGLE, J. 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Howard</au><au>HUTCHINSON, Peter</au><au>OSBORN, Joy</au><au>QIANG HUANG</au><au>POTTER, Linda</au><au>HANCOX, Rachael A</au><au>FLETCHER, Alan</au><au>SALDANHA, Gerald S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>WNT5A Expression Increases during Melanoma Progression and Correlates with Outcome</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2008-09-15</date><risdate>2008</risdate><volume>14</volume><issue>18</issue><spage>5825</spage><epage>5832</epage><pages>5825-5832</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><coden>CCREF4</coden><abstract>Purpose: Wnt ligands play a major role in development and are important in cancer. Expression microarray analysis correlates one member of this family, WNT5A, to a subclass of melanomas with increased motility and invasion. There are no large studies of clinical samples primarily addressing the importance of WNT5A in melanoma progression or outcome. Therefore, this study aimed to assess the protein expression of WNT5A during melanoma progression and its effect on outcome. Experimental Design: Expression of WNT5A was determined in a series of 59 primary melanomas with matched metastases. To provide a benchmark of progression against which to assess WNT5A, expression of p16 ink4a was analyzed, as this has been previously well documented in melanoma. The effect of WNT5A protein expression on outcome was assessed in 102 melanomas. Results: Cytoplasmic WNT5A showed a trend of increasing expression with melanoma progression ( P = 0.013), whereas there was diminishing p16 ink4a expression ( P = 0.006). Nevi showed relatively strong WNT5A expression. Strong cytoplasmic WNT5A was an independent risk factor for reduced metastasis-free and overall survival in multivariate analysis ( P = 0.001 and 0.003, respectively). Conclusion: Cytoplasmic WNT5A increases with melanoma progression and strong expression is associated with poor outcome.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>18794093</pmid><doi>10.1158/1078-0432.CCR-07-5104</doi><tpages>8</tpages></addata></record>
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source MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection
subjects Antineoplastic agents
Biological and medical sciences
Cell Line, Tumor
Cyclin-Dependent Kinase Inhibitor p16 - metabolism
Cytoplasm - metabolism
Dermatology
Disease Progression
Female
Humans
Male
Medical sciences
melanoma
Melanoma - metabolism
Melanoma - pathology
metastasis
Middle Aged
Neoplasm Metastasis
Pharmacology. Drug treatments
Prognosis
progression
Proto-Oncogene Proteins - metabolism
Skin Neoplasms - metabolism
Skin Neoplasms - pathology
survival
Survival Analysis
Tumors of the skin and soft tissue. Premalignant lesions
Wnt Proteins - metabolism
Wnt-5a Protein
WNT5A
title WNT5A Expression Increases during Melanoma Progression and Correlates with Outcome
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