High expression of the mismatch repair protein MSH6 is associated with poor patient survival in melanoma
The outcome of patients with primary melanoma (PM) cannot be completely explained based on currently adopted clinical-histopathologic criteria. In this study, we evaluated the potential prognostic value of mismatch repair protein expression in PMs. We examined the immunohistochemical staining of mis...
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| Veröffentlicht in: | American journal of clinical pathology 2014-07, Vol.142 (1), p.121-132 |
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| creator | Alvino, Ester Passarelli, Francesca Cannavò, Elda Fortes, Cristina Mastroeni, Simona Caporali, Simona Jiricny, Josef Cappellini, Gian Carlo Antonini Scoppola, Alessandro Marchetti, Paolo Modesti, Andrea D'Atri, Stefania |
| description | The outcome of patients with primary melanoma (PM) cannot be completely explained based on currently adopted clinical-histopathologic criteria. In this study, we evaluated the potential prognostic value of mismatch repair protein expression in PMs.
We examined the immunohistochemical staining of mismatch repair proteins in 18 benign nevi and 101 stage I to III PMs and investigated their association with tumor clinicopathologic variables and melanoma mortality.
Expression of MSH2, MLH1, and PMS2 was high in benign nevi and reduced in a subset of PMs. Conversely, MSH6 expression was absent or extremely low in benign nevi and increased in a subset of PMs. In the multivariate analysis, including sex, age, Breslow thickness, and ulceration, high MSH6 expression in PMs (ie, immunostaining in >20% of tumor cells) was significantly associated with an increased risk of melanoma mortality (relative risk, 3.76; 95% confidence interval, 1.12-12.70).
MSH6 protein expression can be a valuable marker to improve prognosis assessment in PMs. |
| doi_str_mv | 10.1309/AJCPCX2D9YULBBLG |
| format | Article |
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We examined the immunohistochemical staining of mismatch repair proteins in 18 benign nevi and 101 stage I to III PMs and investigated their association with tumor clinicopathologic variables and melanoma mortality.
Expression of MSH2, MLH1, and PMS2 was high in benign nevi and reduced in a subset of PMs. Conversely, MSH6 expression was absent or extremely low in benign nevi and increased in a subset of PMs. In the multivariate analysis, including sex, age, Breslow thickness, and ulceration, high MSH6 expression in PMs (ie, immunostaining in >20% of tumor cells) was significantly associated with an increased risk of melanoma mortality (relative risk, 3.76; 95% confidence interval, 1.12-12.70).
MSH6 protein expression can be a valuable marker to improve prognosis assessment in PMs.</description><identifier>ISSN: 0002-9173</identifier><identifier>EISSN: 1943-7722</identifier><identifier>DOI: 10.1309/AJCPCX2D9YULBBLG</identifier><identifier>PMID: 24926095</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Adaptor Proteins, Signal Transducing - metabolism ; Adenosine Triphosphatases - metabolism ; Adult ; Aged ; DNA Mismatch Repair ; DNA Repair Enzymes - metabolism ; DNA-Binding Proteins - metabolism ; Female ; Humans ; Male ; Melanoma - metabolism ; Melanoma - mortality ; Middle Aged ; Mismatch Repair Endonuclease PMS2 ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein - metabolism ; Nevus - metabolism ; Nuclear Proteins - metabolism ; Prognosis ; Skin Neoplasms - metabolism ; Skin Neoplasms - mortality ; Survival Rate</subject><ispartof>American journal of clinical pathology, 2014-07, Vol.142 (1), p.121-132</ispartof><rights>Copyright© by the American Society for Clinical Pathology.</rights><rights>Copyright American Society for Clinical Pathology Jul 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c369t-15a9b4f81223eadde228c39c631ed75b08ed6480c0170c7923e26c0a0ada43e03</citedby><cites>FETCH-LOGICAL-c369t-15a9b4f81223eadde228c39c631ed75b08ed6480c0170c7923e26c0a0ada43e03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24926095$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Alvino, Ester</creatorcontrib><creatorcontrib>Passarelli, Francesca</creatorcontrib><creatorcontrib>Cannavò, Elda</creatorcontrib><creatorcontrib>Fortes, Cristina</creatorcontrib><creatorcontrib>Mastroeni, Simona</creatorcontrib><creatorcontrib>Caporali, Simona</creatorcontrib><creatorcontrib>Jiricny, Josef</creatorcontrib><creatorcontrib>Cappellini, Gian Carlo Antonini</creatorcontrib><creatorcontrib>Scoppola, Alessandro</creatorcontrib><creatorcontrib>Marchetti, Paolo</creatorcontrib><creatorcontrib>Modesti, Andrea</creatorcontrib><creatorcontrib>D'Atri, Stefania</creatorcontrib><title>High expression of the mismatch repair protein MSH6 is associated with poor patient survival in melanoma</title><title>American journal of clinical pathology</title><addtitle>Am J Clin Pathol</addtitle><description>The outcome of patients with primary melanoma (PM) cannot be completely explained based on currently adopted clinical-histopathologic criteria. In this study, we evaluated the potential prognostic value of mismatch repair protein expression in PMs.
We examined the immunohistochemical staining of mismatch repair proteins in 18 benign nevi and 101 stage I to III PMs and investigated their association with tumor clinicopathologic variables and melanoma mortality.
Expression of MSH2, MLH1, and PMS2 was high in benign nevi and reduced in a subset of PMs. Conversely, MSH6 expression was absent or extremely low in benign nevi and increased in a subset of PMs. In the multivariate analysis, including sex, age, Breslow thickness, and ulceration, high MSH6 expression in PMs (ie, immunostaining in >20% of tumor cells) was significantly associated with an increased risk of melanoma mortality (relative risk, 3.76; 95% confidence interval, 1.12-12.70).
MSH6 protein expression can be a valuable marker to improve prognosis assessment in PMs.</description><subject>Adaptor Proteins, Signal Transducing - metabolism</subject><subject>Adenosine Triphosphatases - metabolism</subject><subject>Adult</subject><subject>Aged</subject><subject>DNA Mismatch Repair</subject><subject>DNA Repair Enzymes - metabolism</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Female</subject><subject>Humans</subject><subject>Male</subject><subject>Melanoma - metabolism</subject><subject>Melanoma - mortality</subject><subject>Middle Aged</subject><subject>Mismatch Repair Endonuclease PMS2</subject><subject>MutL Protein Homolog 1</subject><subject>MutS Homolog 2 Protein - metabolism</subject><subject>Nevus - metabolism</subject><subject>Nuclear Proteins - metabolism</subject><subject>Prognosis</subject><subject>Skin Neoplasms - metabolism</subject><subject>Skin Neoplasms - mortality</subject><subject>Survival Rate</subject><issn>0002-9173</issn><issn>1943-7722</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</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>eNpdkc1PGzEUxC1ERVLg3hOyxIXLwvPHfviYpJQUBbUSINHTyvG-sI6y663tpe1_jxGUA6d3-c1o5g0hXxicMwHqYna9-Ll44F_Vr_vVfL662iNTpqTIypLzfTIFAJ4pVooJ-RzCFoDxCuQBmXCpeAEqn5J2aR9bin8HjyFY11O3obFF2tnQ6Wha6nHQ1tPBu4i2pze3y4LaQHUIzlgdsaF_bGzp4FyCdLTYRxpG_2Sf9I4mQYc73btOH5FPG70LePx2D8n9t8u7xTJb_bj6vpitMiMKFTOWa7WWm4pxLlA3DXJeGaFMIRg2Zb6GCptCVmCAlWBKlSheGNCgGy0FgjgkZ6--KfHvEUOsUxWDu5QC3Rhqlou84KpSRUJPP6BbN_o-pUuUlLKqlCoTBa-U8S4Ej5t68LbT_l_NoH5Zof64QpKcvBmP6w6bd8H_t4tnhSeEAg</recordid><startdate>20140701</startdate><enddate>20140701</enddate><creator>Alvino, Ester</creator><creator>Passarelli, Francesca</creator><creator>Cannavò, Elda</creator><creator>Fortes, Cristina</creator><creator>Mastroeni, Simona</creator><creator>Caporali, Simona</creator><creator>Jiricny, Josef</creator><creator>Cappellini, Gian Carlo Antonini</creator><creator>Scoppola, Alessandro</creator><creator>Marchetti, Paolo</creator><creator>Modesti, Andrea</creator><creator>D'Atri, Stefania</creator><general>Oxford University Press</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>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</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>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope></search><sort><creationdate>20140701</creationdate><title>High expression of the mismatch repair protein MSH6 is associated with poor patient survival in melanoma</title><author>Alvino, Ester ; Passarelli, Francesca ; Cannavò, Elda ; Fortes, Cristina ; Mastroeni, Simona ; Caporali, Simona ; Jiricny, Josef ; Cappellini, Gian Carlo Antonini ; Scoppola, Alessandro ; Marchetti, Paolo ; Modesti, Andrea ; D'Atri, Stefania</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c369t-15a9b4f81223eadde228c39c631ed75b08ed6480c0170c7923e26c0a0ada43e03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adaptor Proteins, Signal Transducing - metabolism</topic><topic>Adenosine Triphosphatases - metabolism</topic><topic>Adult</topic><topic>Aged</topic><topic>DNA Mismatch Repair</topic><topic>DNA Repair Enzymes - metabolism</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Female</topic><topic>Humans</topic><topic>Male</topic><topic>Melanoma - metabolism</topic><topic>Melanoma - mortality</topic><topic>Middle Aged</topic><topic>Mismatch Repair Endonuclease PMS2</topic><topic>MutL Protein Homolog 1</topic><topic>MutS Homolog 2 Protein - metabolism</topic><topic>Nevus - metabolism</topic><topic>Nuclear Proteins - metabolism</topic><topic>Prognosis</topic><topic>Skin Neoplasms - metabolism</topic><topic>Skin Neoplasms - mortality</topic><topic>Survival Rate</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Alvino, Ester</creatorcontrib><creatorcontrib>Passarelli, Francesca</creatorcontrib><creatorcontrib>Cannavò, Elda</creatorcontrib><creatorcontrib>Fortes, Cristina</creatorcontrib><creatorcontrib>Mastroeni, Simona</creatorcontrib><creatorcontrib>Caporali, Simona</creatorcontrib><creatorcontrib>Jiricny, Josef</creatorcontrib><creatorcontrib>Cappellini, Gian Carlo Antonini</creatorcontrib><creatorcontrib>Scoppola, Alessandro</creatorcontrib><creatorcontrib>Marchetti, Paolo</creatorcontrib><creatorcontrib>Modesti, Andrea</creatorcontrib><creatorcontrib>D'Atri, Stefania</creatorcontrib><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>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of clinical pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Alvino, Ester</au><au>Passarelli, Francesca</au><au>Cannavò, Elda</au><au>Fortes, Cristina</au><au>Mastroeni, Simona</au><au>Caporali, Simona</au><au>Jiricny, Josef</au><au>Cappellini, Gian Carlo Antonini</au><au>Scoppola, Alessandro</au><au>Marchetti, Paolo</au><au>Modesti, Andrea</au><au>D'Atri, Stefania</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High expression of the mismatch repair protein MSH6 is associated with poor patient survival in melanoma</atitle><jtitle>American journal of clinical pathology</jtitle><addtitle>Am J Clin Pathol</addtitle><date>2014-07-01</date><risdate>2014</risdate><volume>142</volume><issue>1</issue><spage>121</spage><epage>132</epage><pages>121-132</pages><issn>0002-9173</issn><eissn>1943-7722</eissn><abstract>The outcome of patients with primary melanoma (PM) cannot be completely explained based on currently adopted clinical-histopathologic criteria. In this study, we evaluated the potential prognostic value of mismatch repair protein expression in PMs.
We examined the immunohistochemical staining of mismatch repair proteins in 18 benign nevi and 101 stage I to III PMs and investigated their association with tumor clinicopathologic variables and melanoma mortality.
Expression of MSH2, MLH1, and PMS2 was high in benign nevi and reduced in a subset of PMs. Conversely, MSH6 expression was absent or extremely low in benign nevi and increased in a subset of PMs. In the multivariate analysis, including sex, age, Breslow thickness, and ulceration, high MSH6 expression in PMs (ie, immunostaining in >20% of tumor cells) was significantly associated with an increased risk of melanoma mortality (relative risk, 3.76; 95% confidence interval, 1.12-12.70).
MSH6 protein expression can be a valuable marker to improve prognosis assessment in PMs.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>24926095</pmid><doi>10.1309/AJCPCX2D9YULBBLG</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | American journal of clinical pathology, 2014-07, Vol.142 (1), p.121-132 |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals |
| subjects | Adaptor Proteins, Signal Transducing - metabolism Adenosine Triphosphatases - metabolism Adult Aged DNA Mismatch Repair DNA Repair Enzymes - metabolism DNA-Binding Proteins - metabolism Female Humans Male Melanoma - metabolism Melanoma - mortality Middle Aged Mismatch Repair Endonuclease PMS2 MutL Protein Homolog 1 MutS Homolog 2 Protein - metabolism Nevus - metabolism Nuclear Proteins - metabolism Prognosis Skin Neoplasms - metabolism Skin Neoplasms - mortality Survival Rate |
| title | High expression of the mismatch repair protein MSH6 is associated with poor patient survival in melanoma |
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