High survivin mRNA expression is a predictor of poor prognosis in breast cancer: a comparative study at the mRNA and protein level
Background Survivin plays a key role in the initiation and progression of breast cancer. However, its prognostic relevance to breast cancer patients has long been a matter of debate. The purpose of this study was to examine the expression of survivin and its role in predicting clinical outcome in a...
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creator | Xu, Chunsen Yamamoto-Ibusuki, Mutsuko Yamamoto, Yutaka Yamamoto, Satoko Fujiwara, Saori Murakami, Keiichi Okumura, Yasuhiro Yamaguchi, Lisa Fujiki, Yoshitaka Iwase, Hirotaka |
description | Background
Survivin plays a key role in the initiation and progression of breast cancer. However, its prognostic relevance to breast cancer patients has long been a matter of debate. The purpose of this study was to examine the expression of survivin and its role in predicting clinical outcome in a series of human breast cancer cases both at the mRNA and protein level.
Methods
Formalin-fixed paraffin-embedded tumor tissues from 245 female patients with invasive breast cancer and 13 patients with ductal carcinoma in situ were examined for survivin mRNA by quantitative real-time RT-PCR (RT-qPCR). In addition, 237 of these tumors with invasive breast cancer were available for immunohistochemistry (IHC). The relationship between survivin status and clinicopathological characteristics and prognosis was evaluated.
Results
RT-qPCR revealed that high levels of survivin mRNA were strongly associated with high nuclear grade, positive axillary lymph nodes, negative hormone receptor status, positive Her2 amplification, higher Ki67 labeling index, and presence of vascular invasion. In the Cox proportional regression model analysis, survivin mRNA was shown to be a significant univariate parameter for relapse-free survival (RFS), distant relapse-free survival (DRFS), and breast cancer-specific survival (BCSS) as well as a significant multivariate parameter for RFS, DRFS, and BCSS. In hormone receptor (HR)-positive/Her2-negative subtype cases, survivin mRNA expression was also an independent predictor in terms of DRFS. Immunohistochemically, positive staining was seen in the cytoplasm and/or nucleus of cancer cells, although this did not correlate with the mRNA level, and harbored no prognostic value.
Conclusions
High mRNA expression of survivin was an independent marker of poor prognosis both in the entire cohort and in the HR-positive/Her2-negative subtype, whereas the protein expression of survivin was not. These findings suggest that RT-qPCR can provide more reliable data than IHC in validating the prognostic significance of survivin for breast cancer patients. |
doi_str_mv | 10.1007/s12282-012-0403-9 |
format | Article |
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Survivin plays a key role in the initiation and progression of breast cancer. However, its prognostic relevance to breast cancer patients has long been a matter of debate. The purpose of this study was to examine the expression of survivin and its role in predicting clinical outcome in a series of human breast cancer cases both at the mRNA and protein level.
Methods
Formalin-fixed paraffin-embedded tumor tissues from 245 female patients with invasive breast cancer and 13 patients with ductal carcinoma in situ were examined for survivin mRNA by quantitative real-time RT-PCR (RT-qPCR). In addition, 237 of these tumors with invasive breast cancer were available for immunohistochemistry (IHC). The relationship between survivin status and clinicopathological characteristics and prognosis was evaluated.
Results
RT-qPCR revealed that high levels of survivin mRNA were strongly associated with high nuclear grade, positive axillary lymph nodes, negative hormone receptor status, positive Her2 amplification, higher Ki67 labeling index, and presence of vascular invasion. In the Cox proportional regression model analysis, survivin mRNA was shown to be a significant univariate parameter for relapse-free survival (RFS), distant relapse-free survival (DRFS), and breast cancer-specific survival (BCSS) as well as a significant multivariate parameter for RFS, DRFS, and BCSS. In hormone receptor (HR)-positive/Her2-negative subtype cases, survivin mRNA expression was also an independent predictor in terms of DRFS. Immunohistochemically, positive staining was seen in the cytoplasm and/or nucleus of cancer cells, although this did not correlate with the mRNA level, and harbored no prognostic value.
Conclusions
High mRNA expression of survivin was an independent marker of poor prognosis both in the entire cohort and in the HR-positive/Her2-negative subtype, whereas the protein expression of survivin was not. These findings suggest that RT-qPCR can provide more reliable data than IHC in validating the prognostic significance of survivin for breast cancer patients.</description><identifier>ISSN: 1340-6868</identifier><identifier>EISSN: 1880-4233</identifier><identifier>DOI: 10.1007/s12282-012-0403-9</identifier><identifier>PMID: 22968628</identifier><language>eng</language><publisher>Tokyo: Springer Japan</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Analysis ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Breast Neoplasms - mortality ; Breast Neoplasms - pathology ; Cancer ; Cancer patients ; Cancer Research ; Carcinoma, Ductal ; Carcinoma, Ductal, Breast - genetics ; Carcinoma, Ductal, Breast - metabolism ; Carcinoma, Ductal, Breast - mortality ; Carcinoma, Ductal, Breast - secondary ; Carcinoma, Intraductal, Noninfiltrating - genetics ; Carcinoma, Intraductal, Noninfiltrating - metabolism ; Carcinoma, Intraductal, Noninfiltrating - mortality ; Carcinoma, Intraductal, Noninfiltrating - secondary ; Development and progression ; Female ; Follow-Up Studies ; Health aspects ; Humans ; Immunoenzyme Techniques ; Immunohistochemistry ; Inhibitor of Apoptosis Proteins - genetics ; Inhibitor of Apoptosis Proteins - metabolism ; Lymphatic Metastasis ; Medicine ; Medicine & Public Health ; Messenger RNA ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Oncology ; Oncology, Experimental ; Original Article ; Prognosis ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - genetics ; Surgery ; Surgical Oncology ; Survival Rate ; Women</subject><ispartof>Breast cancer (Tokyo, Japan), 2014-07, Vol.21 (4), p.482-490</ispartof><rights>The Japanese Breast Cancer Society 2012</rights><rights>COPYRIGHT 2014 Springer</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c571t-f537bca7f374801628fad863cf1f7a031379d2e6683f97cc17b3b652415405573</citedby><cites>FETCH-LOGICAL-c571t-f537bca7f374801628fad863cf1f7a031379d2e6683f97cc17b3b652415405573</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12282-012-0403-9$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12282-012-0403-9$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22968628$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xu, Chunsen</creatorcontrib><creatorcontrib>Yamamoto-Ibusuki, Mutsuko</creatorcontrib><creatorcontrib>Yamamoto, Yutaka</creatorcontrib><creatorcontrib>Yamamoto, Satoko</creatorcontrib><creatorcontrib>Fujiwara, Saori</creatorcontrib><creatorcontrib>Murakami, Keiichi</creatorcontrib><creatorcontrib>Okumura, Yasuhiro</creatorcontrib><creatorcontrib>Yamaguchi, Lisa</creatorcontrib><creatorcontrib>Fujiki, Yoshitaka</creatorcontrib><creatorcontrib>Iwase, Hirotaka</creatorcontrib><title>High survivin mRNA expression is a predictor of poor prognosis in breast cancer: a comparative study at the mRNA and protein level</title><title>Breast cancer (Tokyo, Japan)</title><addtitle>Breast Cancer</addtitle><addtitle>Breast Cancer</addtitle><description>Background
Survivin plays a key role in the initiation and progression of breast cancer. However, its prognostic relevance to breast cancer patients has long been a matter of debate. The purpose of this study was to examine the expression of survivin and its role in predicting clinical outcome in a series of human breast cancer cases both at the mRNA and protein level.
Methods
Formalin-fixed paraffin-embedded tumor tissues from 245 female patients with invasive breast cancer and 13 patients with ductal carcinoma in situ were examined for survivin mRNA by quantitative real-time RT-PCR (RT-qPCR). In addition, 237 of these tumors with invasive breast cancer were available for immunohistochemistry (IHC). The relationship between survivin status and clinicopathological characteristics and prognosis was evaluated.
Results
RT-qPCR revealed that high levels of survivin mRNA were strongly associated with high nuclear grade, positive axillary lymph nodes, negative hormone receptor status, positive Her2 amplification, higher Ki67 labeling index, and presence of vascular invasion. In the Cox proportional regression model analysis, survivin mRNA was shown to be a significant univariate parameter for relapse-free survival (RFS), distant relapse-free survival (DRFS), and breast cancer-specific survival (BCSS) as well as a significant multivariate parameter for RFS, DRFS, and BCSS. In hormone receptor (HR)-positive/Her2-negative subtype cases, survivin mRNA expression was also an independent predictor in terms of DRFS. Immunohistochemically, positive staining was seen in the cytoplasm and/or nucleus of cancer cells, although this did not correlate with the mRNA level, and harbored no prognostic value.
Conclusions
High mRNA expression of survivin was an independent marker of poor prognosis both in the entire cohort and in the HR-positive/Her2-negative subtype, whereas the protein expression of survivin was not. These findings suggest that RT-qPCR can provide more reliable data than IHC in validating the prognostic significance of survivin for breast cancer patients.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Analysis</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - mortality</subject><subject>Breast Neoplasms - pathology</subject><subject>Cancer</subject><subject>Cancer patients</subject><subject>Cancer Research</subject><subject>Carcinoma, Ductal</subject><subject>Carcinoma, Ductal, Breast - genetics</subject><subject>Carcinoma, Ductal, Breast - metabolism</subject><subject>Carcinoma, Ductal, Breast - mortality</subject><subject>Carcinoma, Ductal, Breast - secondary</subject><subject>Carcinoma, Intraductal, Noninfiltrating - genetics</subject><subject>Carcinoma, Intraductal, Noninfiltrating - metabolism</subject><subject>Carcinoma, Intraductal, Noninfiltrating - mortality</subject><subject>Carcinoma, Intraductal, Noninfiltrating - secondary</subject><subject>Development and progression</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Immunoenzyme Techniques</subject><subject>Immunohistochemistry</subject><subject>Inhibitor of Apoptosis Proteins - genetics</subject><subject>Inhibitor of Apoptosis Proteins - metabolism</subject><subject>Lymphatic Metastasis</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Messenger RNA</subject><subject>Middle Aged</subject><subject>Neoplasm Grading</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplasm Staging</subject><subject>Oncology</subject><subject>Oncology, Experimental</subject><subject>Original Article</subject><subject>Prognosis</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - genetics</subject><subject>Surgery</subject><subject>Surgical Oncology</subject><subject>Survival Rate</subject><subject>Women</subject><issn>1340-6868</issn><issn>1880-4233</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kV1rFTEQhhdRbK3-AG8k4I03W_Oxu8l6dyjVCkVB9Dpks5PTlN1kTbKH9tZf7hy2FgSRECaZed5JmLeqXjN6ziiV7zPjXPGaMtwNFXX_pDplStG64UI8xbNoaN2pTp1UL3K-pbQRknbPqxPOe0xzdVr9uvL7G5LXdPAHH8j87cuOwN2SIGcfA_GZGIK30dsSE4mOLBHjkuI-xIxV1AwJTC7EmmAhfUDexnkxyRR_AJLLOt4TU0i5ga27CeNRXwClExxgelk9c2bK8OohnlU_Pl5-v7iqr79--nyxu65tK1mpXSvkYI10QjaKMvy9M6PqhHXMSUMFE7IfOXSdEq6X1jI5iKFrecPahratFGfVu60vvv5zhVz07LOFaTIB4po1clzgjFiL6NsN3ZsJtA8ulmTsEdc7iUOXXc8YUuf_oHCNMHsbAziP-b8EbBPYFHNO4PSS_GzSvWZUHx3Vm6MaHdVHR3WPmjcPv16HGcZHxR8LEeAbkLEU9pD0bVxTwEn-p-tvN1ip_A</recordid><startdate>20140701</startdate><enddate>20140701</enddate><creator>Xu, Chunsen</creator><creator>Yamamoto-Ibusuki, Mutsuko</creator><creator>Yamamoto, Yutaka</creator><creator>Yamamoto, Satoko</creator><creator>Fujiwara, Saori</creator><creator>Murakami, Keiichi</creator><creator>Okumura, Yasuhiro</creator><creator>Yamaguchi, Lisa</creator><creator>Fujiki, Yoshitaka</creator><creator>Iwase, Hirotaka</creator><general>Springer Japan</general><general>Springer</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>7X8</scope></search><sort><creationdate>20140701</creationdate><title>High survivin mRNA expression is a predictor of poor prognosis in breast cancer: a comparative study at the mRNA and protein level</title><author>Xu, Chunsen ; Yamamoto-Ibusuki, Mutsuko ; Yamamoto, Yutaka ; Yamamoto, Satoko ; Fujiwara, Saori ; Murakami, Keiichi ; Okumura, Yasuhiro ; Yamaguchi, Lisa ; Fujiki, Yoshitaka ; Iwase, Hirotaka</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c571t-f537bca7f374801628fad863cf1f7a031379d2e6683f97cc17b3b652415405573</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Analysis</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - mortality</topic><topic>Breast Neoplasms - pathology</topic><topic>Cancer</topic><topic>Cancer patients</topic><topic>Cancer Research</topic><topic>Carcinoma, Ductal</topic><topic>Carcinoma, Ductal, Breast - genetics</topic><topic>Carcinoma, Ductal, Breast - metabolism</topic><topic>Carcinoma, Ductal, Breast - mortality</topic><topic>Carcinoma, Ductal, Breast - secondary</topic><topic>Carcinoma, Intraductal, Noninfiltrating - genetics</topic><topic>Carcinoma, Intraductal, Noninfiltrating - metabolism</topic><topic>Carcinoma, Intraductal, Noninfiltrating - mortality</topic><topic>Carcinoma, Intraductal, Noninfiltrating - secondary</topic><topic>Development and progression</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Immunoenzyme Techniques</topic><topic>Immunohistochemistry</topic><topic>Inhibitor of Apoptosis Proteins - genetics</topic><topic>Inhibitor of Apoptosis Proteins - metabolism</topic><topic>Lymphatic Metastasis</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Messenger RNA</topic><topic>Middle Aged</topic><topic>Neoplasm Grading</topic><topic>Neoplasm Invasiveness</topic><topic>Neoplasm Staging</topic><topic>Oncology</topic><topic>Oncology, Experimental</topic><topic>Original Article</topic><topic>Prognosis</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - genetics</topic><topic>Surgery</topic><topic>Surgical Oncology</topic><topic>Survival Rate</topic><topic>Women</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xu, Chunsen</creatorcontrib><creatorcontrib>Yamamoto-Ibusuki, Mutsuko</creatorcontrib><creatorcontrib>Yamamoto, Yutaka</creatorcontrib><creatorcontrib>Yamamoto, Satoko</creatorcontrib><creatorcontrib>Fujiwara, Saori</creatorcontrib><creatorcontrib>Murakami, Keiichi</creatorcontrib><creatorcontrib>Okumura, Yasuhiro</creatorcontrib><creatorcontrib>Yamaguchi, Lisa</creatorcontrib><creatorcontrib>Fujiki, Yoshitaka</creatorcontrib><creatorcontrib>Iwase, Hirotaka</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>Breast cancer (Tokyo, Japan)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xu, Chunsen</au><au>Yamamoto-Ibusuki, Mutsuko</au><au>Yamamoto, Yutaka</au><au>Yamamoto, Satoko</au><au>Fujiwara, Saori</au><au>Murakami, Keiichi</au><au>Okumura, Yasuhiro</au><au>Yamaguchi, Lisa</au><au>Fujiki, Yoshitaka</au><au>Iwase, Hirotaka</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High survivin mRNA expression is a predictor of poor prognosis in breast cancer: a comparative study at the mRNA and protein level</atitle><jtitle>Breast cancer (Tokyo, Japan)</jtitle><stitle>Breast Cancer</stitle><addtitle>Breast Cancer</addtitle><date>2014-07-01</date><risdate>2014</risdate><volume>21</volume><issue>4</issue><spage>482</spage><epage>490</epage><pages>482-490</pages><issn>1340-6868</issn><eissn>1880-4233</eissn><abstract>Background
Survivin plays a key role in the initiation and progression of breast cancer. However, its prognostic relevance to breast cancer patients has long been a matter of debate. The purpose of this study was to examine the expression of survivin and its role in predicting clinical outcome in a series of human breast cancer cases both at the mRNA and protein level.
Methods
Formalin-fixed paraffin-embedded tumor tissues from 245 female patients with invasive breast cancer and 13 patients with ductal carcinoma in situ were examined for survivin mRNA by quantitative real-time RT-PCR (RT-qPCR). In addition, 237 of these tumors with invasive breast cancer were available for immunohistochemistry (IHC). The relationship between survivin status and clinicopathological characteristics and prognosis was evaluated.
Results
RT-qPCR revealed that high levels of survivin mRNA were strongly associated with high nuclear grade, positive axillary lymph nodes, negative hormone receptor status, positive Her2 amplification, higher Ki67 labeling index, and presence of vascular invasion. In the Cox proportional regression model analysis, survivin mRNA was shown to be a significant univariate parameter for relapse-free survival (RFS), distant relapse-free survival (DRFS), and breast cancer-specific survival (BCSS) as well as a significant multivariate parameter for RFS, DRFS, and BCSS. In hormone receptor (HR)-positive/Her2-negative subtype cases, survivin mRNA expression was also an independent predictor in terms of DRFS. Immunohistochemically, positive staining was seen in the cytoplasm and/or nucleus of cancer cells, although this did not correlate with the mRNA level, and harbored no prognostic value.
Conclusions
High mRNA expression of survivin was an independent marker of poor prognosis both in the entire cohort and in the HR-positive/Her2-negative subtype, whereas the protein expression of survivin was not. These findings suggest that RT-qPCR can provide more reliable data than IHC in validating the prognostic significance of survivin for breast cancer patients.</abstract><cop>Tokyo</cop><pub>Springer Japan</pub><pmid>22968628</pmid><doi>10.1007/s12282-012-0403-9</doi><tpages>9</tpages></addata></record> |
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subjects | Adult Aged Aged, 80 and over Analysis Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Breast Neoplasms - genetics Breast Neoplasms - metabolism Breast Neoplasms - mortality Breast Neoplasms - pathology Cancer Cancer patients Cancer Research Carcinoma, Ductal Carcinoma, Ductal, Breast - genetics Carcinoma, Ductal, Breast - metabolism Carcinoma, Ductal, Breast - mortality Carcinoma, Ductal, Breast - secondary Carcinoma, Intraductal, Noninfiltrating - genetics Carcinoma, Intraductal, Noninfiltrating - metabolism Carcinoma, Intraductal, Noninfiltrating - mortality Carcinoma, Intraductal, Noninfiltrating - secondary Development and progression Female Follow-Up Studies Health aspects Humans Immunoenzyme Techniques Immunohistochemistry Inhibitor of Apoptosis Proteins - genetics Inhibitor of Apoptosis Proteins - metabolism Lymphatic Metastasis Medicine Medicine & Public Health Messenger RNA Middle Aged Neoplasm Grading Neoplasm Invasiveness Neoplasm Staging Oncology Oncology, Experimental Original Article Prognosis Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics Surgery Surgical Oncology Survival Rate Women |
title | High survivin mRNA expression is a predictor of poor prognosis in breast cancer: a comparative study at the mRNA and protein level |
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