Tissue Microarray Analysis of Signal Transducers and Activators of Transcription 3 (Stat3) and Phospho-Stat3 (Tyr705) in Node-negative Breast Cancer Shows Nuclear Localization Is Associated with a Better Prognosis

Purpose: Although a high frequency of tumors contain constitutively activated signal transducers and activators of transcription 3 (Stat3), its relationship to breast cancer and patient survival has not been determined in a large retrospective study of node-negative tumors. To further elucidate the...

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Veröffentlicht in:Clinical cancer research 2003-02, Vol.9 (2), p.594-600
Hauptverfasser: DOLLED-FILHART, Marisa, CAMP, Robert L, KOWALSKI, Diane P, SMITH, Bradley L, RIMM, David L
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container_issue 2
container_start_page 594
container_title Clinical cancer research
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creator DOLLED-FILHART, Marisa
CAMP, Robert L
KOWALSKI, Diane P
SMITH, Bradley L
RIMM, David L
description Purpose: Although a high frequency of tumors contain constitutively activated signal transducers and activators of transcription 3 (Stat3), its relationship to breast cancer and patient survival has not been determined in a large retrospective study of node-negative tumors. To further elucidate the role of Stat3 in breast cancers, the expression patterns of Stat3 and Phospho-tyrosine residue 705 (Tyr705) Stat3 were correlated with survival outcome and clinicopathological parameters in a large cohort of node-negative breast cancer tumors. Experimental Design: Immunohistochemical analysis of Stat3 and Phospho-Stat3 was performed on a breast cancer tissue microarray of 346 node-negative breast cancer specimens. These results were correlated with overall survival and other clinicopathological data. Results : Positive Stat3 cytoplasmic expression was seen in 69.2% of tumors, and positive Phospho-Stat3 (Tyr705) cytoplasmic expression was seen in 19.6% of tumors. Neither cytoplasmic expression showed significant association with survival or other clinical parameters. However, 23.1% of tumors had positive Stat3 nuclear expression, and those patients had a significantly improved short-term survival ( P = 0.0332) at 5 years of follow-up. Upon analysis of positive Phospho-Stat3 (Tyr705) nuclear expression, seen in 43.5% of tumors, positive tumors had a significantly improved survival at both short-term 5-year survival ( P = 0.0054) and long-term 20-year ( P = 0.0376) survival analysis. Additionally, positive Phospho-Stat3 (Tyr705) nuclear expression is an independent prognostic marker of better overall survival node-negative breast cancer by multivariate analyses that included the variables of nuclear grade, Ki-67, estrogen receptor staining, progesterone receptor staining, Her2 staining, age, and tumor size. Conclusions: These findings support a role for Stat3 and Phospho-Stat3 (Tyr705) overexpression in node-negative breast cancer and provide initial evidence that Phospho-Stat3 (Tyr705) may be a marker for improved overall survival independent of other prognostic markers.
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To further elucidate the role of Stat3 in breast cancers, the expression patterns of Stat3 and Phospho-tyrosine residue 705 (Tyr705) Stat3 were correlated with survival outcome and clinicopathological parameters in a large cohort of node-negative breast cancer tumors. Experimental Design: Immunohistochemical analysis of Stat3 and Phospho-Stat3 was performed on a breast cancer tissue microarray of 346 node-negative breast cancer specimens. These results were correlated with overall survival and other clinicopathological data. Results : Positive Stat3 cytoplasmic expression was seen in 69.2% of tumors, and positive Phospho-Stat3 (Tyr705) cytoplasmic expression was seen in 19.6% of tumors. Neither cytoplasmic expression showed significant association with survival or other clinical parameters. However, 23.1% of tumors had positive Stat3 nuclear expression, and those patients had a significantly improved short-term survival ( P = 0.0332) at 5 years of follow-up. Upon analysis of positive Phospho-Stat3 (Tyr705) nuclear expression, seen in 43.5% of tumors, positive tumors had a significantly improved survival at both short-term 5-year survival ( P = 0.0054) and long-term 20-year ( P = 0.0376) survival analysis. Additionally, positive Phospho-Stat3 (Tyr705) nuclear expression is an independent prognostic marker of better overall survival node-negative breast cancer by multivariate analyses that included the variables of nuclear grade, Ki-67, estrogen receptor staining, progesterone receptor staining, Her2 staining, age, and tumor size. 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Obstetrics ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Mammary gland diseases ; Medical sciences ; Multivariate Analysis ; Phosphorylation ; Phosphotyrosine - analysis ; Prognosis ; Proportional Hazards Models ; STAT3 Transcription Factor ; Survival Analysis ; Time Factors ; Trans-Activators - metabolism ; Tumors</subject><ispartof>Clinical cancer research, 2003-02, Vol.9 (2), p.594-600</ispartof><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=14544696$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12576423$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>DOLLED-FILHART, Marisa</creatorcontrib><creatorcontrib>CAMP, Robert L</creatorcontrib><creatorcontrib>KOWALSKI, Diane P</creatorcontrib><creatorcontrib>SMITH, Bradley L</creatorcontrib><creatorcontrib>RIMM, David L</creatorcontrib><title>Tissue Microarray Analysis of Signal Transducers and Activators of Transcription 3 (Stat3) and Phospho-Stat3 (Tyr705) in Node-negative Breast Cancer Shows Nuclear Localization Is Associated with a Better Prognosis</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Purpose: Although a high frequency of tumors contain constitutively activated signal transducers and activators of transcription 3 (Stat3), its relationship to breast cancer and patient survival has not been determined in a large retrospective study of node-negative tumors. 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Upon analysis of positive Phospho-Stat3 (Tyr705) nuclear expression, seen in 43.5% of tumors, positive tumors had a significantly improved survival at both short-term 5-year survival ( P = 0.0054) and long-term 20-year ( P = 0.0376) survival analysis. Additionally, positive Phospho-Stat3 (Tyr705) nuclear expression is an independent prognostic marker of better overall survival node-negative breast cancer by multivariate analyses that included the variables of nuclear grade, Ki-67, estrogen receptor staining, progesterone receptor staining, Her2 staining, age, and tumor size. Conclusions: These findings support a role for Stat3 and Phospho-Stat3 (Tyr705) overexpression in node-negative breast cancer and provide initial evidence that Phospho-Stat3 (Tyr705) may be a marker for improved overall survival independent of other prognostic markers.</description><subject>Acute-Phase Proteins - analysis</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - analysis</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - mortality</subject><subject>Breast Neoplasms - pathology</subject><subject>Cell Nucleus - metabolism</subject><subject>Cell Nucleus - pathology</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Female</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Lymphatic Metastasis</subject><subject>Mammary gland diseases</subject><subject>Medical sciences</subject><subject>Multivariate Analysis</subject><subject>Phosphorylation</subject><subject>Phosphotyrosine - analysis</subject><subject>Prognosis</subject><subject>Proportional Hazards Models</subject><subject>STAT3 Transcription Factor</subject><subject>Survival Analysis</subject><subject>Time Factors</subject><subject>Trans-Activators - metabolism</subject><subject>Tumors</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkc9u2zAMxo1iQ9u1e4WBlw3twYCtP3Z8TINuK5C1BZKdDUamYw2OlYnyguw9-z4VvAw9CJSoHz9KH8-Sy1zrMpWi0O_iPitnaaakuEg-MP_KslzlmTpPLnKhy0IJeZm8rC3zSPDDGu_QezzCfMD-yJbBtbCy23iCtceBm9GQZ8ChgbkJ9g8G5ydoujXe7oN1A0i4WQUM8nYinzvH-86lUwpu1kdfZvoW7ACPrqF0oC1GKYI7T8gBFjjEJrDq3IHhcTQ9oYelM9jbvzjJPzDMmZ2xGKiBgw0dINxRCLHs2bvt4OLTr5P3LfZMH0_xKvn59X69-J4un749LObLtBPFLKRKt6JpKiE1VkSVarFqhMFC5HGpUm0EVTNUBRoqC0N5rgs5y5Vq5UZqWaG8Sr78091793skDvXOsqG-x4HcyHUpsziPTEfw0wkcNztq6r23O_TH-v8gIvD5BCDH37bRUmP5jVNaqaIq3jp2dtsdrKfaTJZ54miV6eqqFrWulHwF7rSiZg</recordid><startdate>20030201</startdate><enddate>20030201</enddate><creator>DOLLED-FILHART, Marisa</creator><creator>CAMP, Robert L</creator><creator>KOWALSKI, Diane P</creator><creator>SMITH, Bradley L</creator><creator>RIMM, David L</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20030201</creationdate><title>Tissue Microarray Analysis of Signal Transducers and Activators of Transcription 3 (Stat3) and Phospho-Stat3 (Tyr705) in Node-negative Breast Cancer Shows Nuclear Localization Is Associated with a Better Prognosis</title><author>DOLLED-FILHART, Marisa ; CAMP, Robert L ; KOWALSKI, Diane P ; SMITH, Bradley L ; RIMM, David L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h268t-45f2dd9235a9ee94fa9d2ca621a62474b2e98a46ace76ce115638144f3b3539a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Acute-Phase Proteins - analysis</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - analysis</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - mortality</topic><topic>Breast Neoplasms - pathology</topic><topic>Cell Nucleus - metabolism</topic><topic>Cell Nucleus - pathology</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Female</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Lymphatic Metastasis</topic><topic>Mammary gland diseases</topic><topic>Medical sciences</topic><topic>Multivariate Analysis</topic><topic>Phosphorylation</topic><topic>Phosphotyrosine - analysis</topic><topic>Prognosis</topic><topic>Proportional Hazards Models</topic><topic>STAT3 Transcription Factor</topic><topic>Survival Analysis</topic><topic>Time Factors</topic><topic>Trans-Activators - metabolism</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>DOLLED-FILHART, Marisa</creatorcontrib><creatorcontrib>CAMP, Robert L</creatorcontrib><creatorcontrib>KOWALSKI, Diane P</creatorcontrib><creatorcontrib>SMITH, Bradley L</creatorcontrib><creatorcontrib>RIMM, David L</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>DOLLED-FILHART, Marisa</au><au>CAMP, Robert L</au><au>KOWALSKI, Diane P</au><au>SMITH, Bradley L</au><au>RIMM, David L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tissue Microarray Analysis of Signal Transducers and Activators of Transcription 3 (Stat3) and Phospho-Stat3 (Tyr705) in Node-negative Breast Cancer Shows Nuclear Localization Is Associated with a Better Prognosis</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2003-02-01</date><risdate>2003</risdate><volume>9</volume><issue>2</issue><spage>594</spage><epage>600</epage><pages>594-600</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Purpose: Although a high frequency of tumors contain constitutively activated signal transducers and activators of transcription 3 (Stat3), its relationship to breast cancer and patient survival has not been determined in a large retrospective study of node-negative tumors. To further elucidate the role of Stat3 in breast cancers, the expression patterns of Stat3 and Phospho-tyrosine residue 705 (Tyr705) Stat3 were correlated with survival outcome and clinicopathological parameters in a large cohort of node-negative breast cancer tumors. Experimental Design: Immunohistochemical analysis of Stat3 and Phospho-Stat3 was performed on a breast cancer tissue microarray of 346 node-negative breast cancer specimens. These results were correlated with overall survival and other clinicopathological data. Results : Positive Stat3 cytoplasmic expression was seen in 69.2% of tumors, and positive Phospho-Stat3 (Tyr705) cytoplasmic expression was seen in 19.6% of tumors. Neither cytoplasmic expression showed significant association with survival or other clinical parameters. However, 23.1% of tumors had positive Stat3 nuclear expression, and those patients had a significantly improved short-term survival ( P = 0.0332) at 5 years of follow-up. Upon analysis of positive Phospho-Stat3 (Tyr705) nuclear expression, seen in 43.5% of tumors, positive tumors had a significantly improved survival at both short-term 5-year survival ( P = 0.0054) and long-term 20-year ( P = 0.0376) survival analysis. Additionally, positive Phospho-Stat3 (Tyr705) nuclear expression is an independent prognostic marker of better overall survival node-negative breast cancer by multivariate analyses that included the variables of nuclear grade, Ki-67, estrogen receptor staining, progesterone receptor staining, Her2 staining, age, and tumor size. Conclusions: These findings support a role for Stat3 and Phospho-Stat3 (Tyr705) overexpression in node-negative breast cancer and provide initial evidence that Phospho-Stat3 (Tyr705) may be a marker for improved overall survival independent of other prognostic markers.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>12576423</pmid><tpages>7</tpages></addata></record>
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ispartof Clinical cancer research, 2003-02, Vol.9 (2), p.594-600
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source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; American Association for Cancer Research; Alma/SFX Local Collection
subjects Acute-Phase Proteins - analysis
Biological and medical sciences
Biomarkers - analysis
Breast Neoplasms - metabolism
Breast Neoplasms - mortality
Breast Neoplasms - pathology
Cell Nucleus - metabolism
Cell Nucleus - pathology
DNA-Binding Proteins - metabolism
Female
Gynecology. Andrology. Obstetrics
Humans
Immunohistochemistry
Lymphatic Metastasis
Mammary gland diseases
Medical sciences
Multivariate Analysis
Phosphorylation
Phosphotyrosine - analysis
Prognosis
Proportional Hazards Models
STAT3 Transcription Factor
Survival Analysis
Time Factors
Trans-Activators - metabolism
Tumors
title Tissue Microarray Analysis of Signal Transducers and Activators of Transcription 3 (Stat3) and Phospho-Stat3 (Tyr705) in Node-negative Breast Cancer Shows Nuclear Localization Is Associated with a Better Prognosis
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