Reduced RKIP Expression is Associated With Breast Neoplastic Progression and is Correlated With Poor Outcomes and Aberrant Methylation in Breast Carcinoma
Raf kinase inhibitor protein's (RKIP) downregulation can predict poor outcome in patients with various types of malignancy. In this study, we aimed to assess the potential involvement of RKIP in breast carcinogenesis and to evaluate its association with outcome variables and aberrant promoter m...
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| Veröffentlicht in: | Applied immunohistochemistry & molecular morphology 2017-08, Vol.25 (7), p.467-474 |
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| creator | Kim, Ga-Eon Kim, Nah Ihm Lee, Ji Shin Park, Min Ho Yoon, Jung Han |
| description | Raf kinase inhibitor protein's (RKIP) downregulation can predict poor outcome in patients with various types of malignancy. In this study, we aimed to assess the potential involvement of RKIP in breast carcinogenesis and to evaluate its association with outcome variables and aberrant promoter methylation in breast carcinoma (BC). Tissue microarray sections were immunostained for RKIP in 26 normal breasts, 25 usual ductal hyperplasia, 76 ductal carcinoma in situ, and 198 BC specimens. The methylation status of RKIP was also determined in BC. In addition, the mRNA and protein level of RKIP was analyzed in 8 pairs of BC tissues and surrounding normal tissues by quantitative real-time polymerase chain reaction and Western blot analysis, respectively. RKIP mRNA and protein expression was significantly downregulated in BC tissues compared with the surrounding normal tissues (P |
| doi_str_mv | 10.1097/PAI.0000000000000323 |
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In this study, we aimed to assess the potential involvement of RKIP in breast carcinogenesis and to evaluate its association with outcome variables and aberrant promoter methylation in breast carcinoma (BC). Tissue microarray sections were immunostained for RKIP in 26 normal breasts, 25 usual ductal hyperplasia, 76 ductal carcinoma in situ, and 198 BC specimens. The methylation status of RKIP was also determined in BC. In addition, the mRNA and protein level of RKIP was analyzed in 8 pairs of BC tissues and surrounding normal tissues by quantitative real-time polymerase chain reaction and Western blot analysis, respectively. RKIP mRNA and protein expression was significantly downregulated in BC tissues compared with the surrounding normal tissues (P<0.05 and P<0.01, respectively). Reduced RKIP expression seemed to increase progressively from normal breast to BC (P<0.001). Reduced RKIP expression was significantly associated with metastatic relapse (P<0.001) and was identified as an independent adverse prognostic indicator for disease-free survival (P=0.003). Reduced RKIP expression in BC was significantly correlated with its aberrant promoter methylation (P<0.05). In conclusion, downregulation of RKIP plays an important role in the breast neoplastic progression and correlates with poor prognosis in patients with BC. Aberrant RKIP methylation is one of the mechanisms that lead to downregulation of RKIP in BC.</description><identifier>ISSN: 1541-2016</identifier><identifier>EISSN: 1533-4058</identifier><identifier>DOI: 10.1097/PAI.0000000000000323</identifier><identifier>PMID: 26894644</identifier><language>eng</language><publisher>United States</publisher><subject>Adult ; Aged ; Breast Neoplasms - metabolism ; Breast Neoplasms - mortality ; Breast Neoplasms - pathology ; Carcinoma, Intraductal, Noninfiltrating - metabolism ; Carcinoma, Intraductal, Noninfiltrating - mortality ; Carcinoma, Intraductal, Noninfiltrating - pathology ; Disease-Free Survival ; DNA Methylation ; DNA, Neoplasm - metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Neoplasm Proteins - biosynthesis ; Phosphatidylethanolamine Binding Protein - biosynthesis ; Survival Rate</subject><ispartof>Applied immunohistochemistry & molecular morphology, 2017-08, Vol.25 (7), p.467-474</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c307t-aaa2639bb99a5a11b9d639502f0b18028ec39de32ae0b4920d269010c69b87623</citedby><cites>FETCH-LOGICAL-c307t-aaa2639bb99a5a11b9d639502f0b18028ec39de32ae0b4920d269010c69b87623</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27907,27908</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26894644$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Ga-Eon</creatorcontrib><creatorcontrib>Kim, Nah Ihm</creatorcontrib><creatorcontrib>Lee, Ji Shin</creatorcontrib><creatorcontrib>Park, Min Ho</creatorcontrib><creatorcontrib>Yoon, Jung Han</creatorcontrib><title>Reduced RKIP Expression is Associated With Breast Neoplastic Progression and is Correlated With Poor Outcomes and Aberrant Methylation in Breast Carcinoma</title><title>Applied immunohistochemistry & molecular morphology</title><addtitle>Appl Immunohistochem Mol Morphol</addtitle><description>Raf kinase inhibitor protein's (RKIP) downregulation can predict poor outcome in patients with various types of malignancy. In this study, we aimed to assess the potential involvement of RKIP in breast carcinogenesis and to evaluate its association with outcome variables and aberrant promoter methylation in breast carcinoma (BC). Tissue microarray sections were immunostained for RKIP in 26 normal breasts, 25 usual ductal hyperplasia, 76 ductal carcinoma in situ, and 198 BC specimens. The methylation status of RKIP was also determined in BC. In addition, the mRNA and protein level of RKIP was analyzed in 8 pairs of BC tissues and surrounding normal tissues by quantitative real-time polymerase chain reaction and Western blot analysis, respectively. RKIP mRNA and protein expression was significantly downregulated in BC tissues compared with the surrounding normal tissues (P<0.05 and P<0.01, respectively). Reduced RKIP expression seemed to increase progressively from normal breast to BC (P<0.001). Reduced RKIP expression was significantly associated with metastatic relapse (P<0.001) and was identified as an independent adverse prognostic indicator for disease-free survival (P=0.003). Reduced RKIP expression in BC was significantly correlated with its aberrant promoter methylation (P<0.05). In conclusion, downregulation of RKIP plays an important role in the breast neoplastic progression and correlates with poor prognosis in patients with BC. Aberrant RKIP methylation is one of the mechanisms that lead to downregulation of RKIP in BC.</description><subject>Adult</subject><subject>Aged</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - mortality</subject><subject>Breast Neoplasms - pathology</subject><subject>Carcinoma, Intraductal, Noninfiltrating - metabolism</subject><subject>Carcinoma, Intraductal, Noninfiltrating - mortality</subject><subject>Carcinoma, Intraductal, Noninfiltrating - pathology</subject><subject>Disease-Free Survival</subject><subject>DNA Methylation</subject><subject>DNA, Neoplasm - metabolism</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Middle Aged</subject><subject>Neoplasm Proteins - biosynthesis</subject><subject>Phosphatidylethanolamine Binding Protein - biosynthesis</subject><subject>Survival Rate</subject><issn>1541-2016</issn><issn>1533-4058</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkctOwzAQRS0EolD4A4S8ZJPiV9x4WaoCFYVGFYhl5DhTGpTExU4k-it8LekLELOZGc09dxYXoQtKepSo_nU8GPfI3-KMH6ATGnIeCBJGh-tZ0IARKjvo1Pt3QhjjQhyjDpORElKIE_Q1g6wxkOHZwzjGo8-lA-9zW-Hc44H31uS6bq-veb3ANw60r_ET2GXRDrnBsbNve0BX2RoaWueg-IViax2eNrWxJfiNaJCCc7qq8SPUi1Ur3byr9vZD7Uxe2VKfoaO5Ljyc73oXvdyOnof3wWR6Nx4OJoHhpF8HWmsmuUpTpXSoKU1V1q4hYXOS0oiwCAxXGXCmgaRCMZIxqQglRqo06kvGu-hq67t09qMBXydl7g0Uha7ANj6hEZMypJEIW6nYSo2z3juYJ0uXl9qtEkqSdSpJm0ryP5UWu9x9aNISsh9oHwP_BvIniQU</recordid><startdate>20170801</startdate><enddate>20170801</enddate><creator>Kim, Ga-Eon</creator><creator>Kim, Nah Ihm</creator><creator>Lee, Ji Shin</creator><creator>Park, Min Ho</creator><creator>Yoon, Jung Han</creator><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>20170801</creationdate><title>Reduced RKIP Expression is Associated With Breast Neoplastic Progression and is Correlated With Poor Outcomes and Aberrant Methylation in Breast Carcinoma</title><author>Kim, Ga-Eon ; Kim, Nah Ihm ; Lee, Ji Shin ; Park, Min Ho ; Yoon, Jung Han</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c307t-aaa2639bb99a5a11b9d639502f0b18028ec39de32ae0b4920d269010c69b87623</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - mortality</topic><topic>Breast Neoplasms - pathology</topic><topic>Carcinoma, Intraductal, Noninfiltrating - metabolism</topic><topic>Carcinoma, Intraductal, Noninfiltrating - mortality</topic><topic>Carcinoma, Intraductal, Noninfiltrating - pathology</topic><topic>Disease-Free Survival</topic><topic>DNA Methylation</topic><topic>DNA, Neoplasm - metabolism</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Middle Aged</topic><topic>Neoplasm Proteins - biosynthesis</topic><topic>Phosphatidylethanolamine Binding Protein - biosynthesis</topic><topic>Survival Rate</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Ga-Eon</creatorcontrib><creatorcontrib>Kim, Nah Ihm</creatorcontrib><creatorcontrib>Lee, Ji Shin</creatorcontrib><creatorcontrib>Park, Min Ho</creatorcontrib><creatorcontrib>Yoon, Jung Han</creatorcontrib><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>Applied immunohistochemistry & molecular morphology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Ga-Eon</au><au>Kim, Nah Ihm</au><au>Lee, Ji Shin</au><au>Park, Min Ho</au><au>Yoon, Jung Han</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reduced RKIP Expression is Associated With Breast Neoplastic Progression and is Correlated With Poor Outcomes and Aberrant Methylation in Breast Carcinoma</atitle><jtitle>Applied immunohistochemistry & molecular morphology</jtitle><addtitle>Appl Immunohistochem Mol Morphol</addtitle><date>2017-08-01</date><risdate>2017</risdate><volume>25</volume><issue>7</issue><spage>467</spage><epage>474</epage><pages>467-474</pages><issn>1541-2016</issn><eissn>1533-4058</eissn><abstract>Raf kinase inhibitor protein's (RKIP) downregulation can predict poor outcome in patients with various types of malignancy. In this study, we aimed to assess the potential involvement of RKIP in breast carcinogenesis and to evaluate its association with outcome variables and aberrant promoter methylation in breast carcinoma (BC). Tissue microarray sections were immunostained for RKIP in 26 normal breasts, 25 usual ductal hyperplasia, 76 ductal carcinoma in situ, and 198 BC specimens. The methylation status of RKIP was also determined in BC. In addition, the mRNA and protein level of RKIP was analyzed in 8 pairs of BC tissues and surrounding normal tissues by quantitative real-time polymerase chain reaction and Western blot analysis, respectively. RKIP mRNA and protein expression was significantly downregulated in BC tissues compared with the surrounding normal tissues (P<0.05 and P<0.01, respectively). Reduced RKIP expression seemed to increase progressively from normal breast to BC (P<0.001). Reduced RKIP expression was significantly associated with metastatic relapse (P<0.001) and was identified as an independent adverse prognostic indicator for disease-free survival (P=0.003). Reduced RKIP expression in BC was significantly correlated with its aberrant promoter methylation (P<0.05). In conclusion, downregulation of RKIP plays an important role in the breast neoplastic progression and correlates with poor prognosis in patients with BC. Aberrant RKIP methylation is one of the mechanisms that lead to downregulation of RKIP in BC.</abstract><cop>United States</cop><pmid>26894644</pmid><doi>10.1097/PAI.0000000000000323</doi><tpages>8</tpages></addata></record> |
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| subjects | Adult Aged Breast Neoplasms - metabolism Breast Neoplasms - mortality Breast Neoplasms - pathology Carcinoma, Intraductal, Noninfiltrating - metabolism Carcinoma, Intraductal, Noninfiltrating - mortality Carcinoma, Intraductal, Noninfiltrating - pathology Disease-Free Survival DNA Methylation DNA, Neoplasm - metabolism Female Gene Expression Regulation, Neoplastic Humans Middle Aged Neoplasm Proteins - biosynthesis Phosphatidylethanolamine Binding Protein - biosynthesis Survival Rate |
| title | Reduced RKIP Expression is Associated With Breast Neoplastic Progression and is Correlated With Poor Outcomes and Aberrant Methylation in Breast Carcinoma |
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