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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Veröffentlicht in:Breast cancer (Tokyo, Japan) Japan), 2014-07, Vol.21 (4), p.482-490
Hauptverfasser: Xu, Chunsen, Yamamoto-Ibusuki, Mutsuko, Yamamoto, Yutaka, Yamamoto, Satoko, Fujiwara, Saori, Murakami, Keiichi, Okumura, Yasuhiro, Yamaguchi, Lisa, Fujiki, Yoshitaka, Iwase, Hirotaka
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container_end_page 490
container_issue 4
container_start_page 482
container_title Breast cancer (Tokyo, Japan)
container_volume 21
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
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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 &amp; 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 &amp; 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 &amp; 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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identifier ISSN: 1340-6868
ispartof Breast cancer (Tokyo, Japan), 2014-07, Vol.21 (4), p.482-490
issn 1340-6868
1880-4233
language eng
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source MEDLINE; SpringerLink Journals - AutoHoldings
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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