Tissue Microarray Analysis of β-Catenin in Colorectal Cancer Shows Nuclear Phospho-β-catenin Is Associated with a Better Prognosis
Purpose : β-Catenin is involved in homotypic cell-cell adhesion and the wnt signaling pathway. Deregulation of β-catenin levels, caused in part by mutations of the adenomatous polyposis coli gene, is thought to play a role in the development of colorectal and other cancers. To further elucidate thei...
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| Veröffentlicht in: | Clinical cancer research 2001-12, Vol.7 (12), p.4013-4020 |
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| creator | CHUNG, Gina G PROVOST, Elayne KIELHORN, Eric P CHARETTE, Lori A SMITH, Bradley L RIMM, David L |
| description | Purpose : β-Catenin is involved in homotypic cell-cell adhesion and the wnt signaling pathway. Deregulation of β-catenin levels, caused in part by mutations of the adenomatous polyposis coli gene,
is thought to play a role in the development of colorectal and other cancers. To further elucidate their roles, the expression
pattern of β-catenin and phosphospecific β-catenin was correlated with clinical outcome in a series of patients with colorectal
cancer.
Experimental Design: Immunohistochemical analysis of a tissue microarray with 650 colorectal cancer specimens was performed to study the expression
and subcellular localization of β-catenin and phosphospecific β-catenin. These results were correlated with other clinicopathological
factors and with overall survival.
Results: The majority of cancers retained some degree of β-catenin membranous staining, whereas cytoplasmic or nuclear expression
was seen in 42.5% and 20.4% of specimens, respectively. Phospho-β-catenin showed nuclear staining in 9.5% of specimens, and
there was no apparent membranous or cytoplasmic staining. There was no significant association between β-catenin or phospho-β-catenin
and grade or stage. However, there was a positive correlation between β-catenin and phospho-β-catenin ( P = 0.039), with phospho-β-catenin representing a subset of nuclear β-catenin. Patients with nuclear expression of β-catenin
did not have an altered survival compared with those that did not ( P = 0.5611). Nuclear expression of phospho-β-catenin, however, was associated with an improved survival ( P = 0.0006). In multivariate analysis, only stage and phospho-β-catenin were independently predictive of overall survival ( P < 0.001 and P = 0.0034, respectively).
Conclusions: These findings support a role for β-catenin overexpression in colorectal tumorigenesis and provide initial evidence that
phospho-β-catenin may be a marker for improved overall survival independent of stage and grade. |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_72367590</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>72367590</sourcerecordid><originalsourceid>FETCH-LOGICAL-h270t-49224c5f5b02741641971e2c5d4727cb0904054d843dfff1ad3dbee402cc33d43</originalsourceid><addsrcrecordid>eNpFkNtKw0AQhoMotlZfQfZG8Sawx25zWYOHQtWC9TpsNptmZZutOwml9z6RD-IzudSKMDAz8P0z8B0lQyKETBkdi-M4YzlJMWd0kJwBvGNMOMH8NBkQIgXhmRgmn0sL0Bv0ZHXwKgS1Q9NWuR1YQL5G319prjrT2hbFyr3zwehOOZSrVpuAXhu_BfTca2dUQIvGw6bxaUzpQ2oGaArgtY17hba2a5BCt6brYngR_Kr18dN5clIrB-bi0EfJ2_3dMn9M5y8Ps3w6TxsqcZfyjFKuRS1KTCUnY04ySQzVouKSSl3iDHMseDXhrKrrmqiKVaUxHFOtGas4GyXXv3c3wX_0BrpibUEb51RrfA-FpGwsRYYjeHkA-3JtqmIT7FqFXfHnLQJXB0CBVq4OUYeFf45xItj-0M0v19hVs7XBFHovLhiIwnRTyILQgmPC2A8-kody</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>72367590</pqid></control><display><type>article</type><title>Tissue Microarray Analysis of β-Catenin in Colorectal Cancer Shows Nuclear Phospho-β-catenin Is Associated with a Better Prognosis</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>CHUNG, Gina G ; PROVOST, Elayne ; KIELHORN, Eric P ; CHARETTE, Lori A ; SMITH, Bradley L ; RIMM, David L</creator><creatorcontrib>CHUNG, Gina G ; PROVOST, Elayne ; KIELHORN, Eric P ; CHARETTE, Lori A ; SMITH, Bradley L ; RIMM, David L</creatorcontrib><description>Purpose : β-Catenin is involved in homotypic cell-cell adhesion and the wnt signaling pathway. Deregulation of β-catenin levels, caused in part by mutations of the adenomatous polyposis coli gene,
is thought to play a role in the development of colorectal and other cancers. To further elucidate their roles, the expression
pattern of β-catenin and phosphospecific β-catenin was correlated with clinical outcome in a series of patients with colorectal
cancer.
Experimental Design: Immunohistochemical analysis of a tissue microarray with 650 colorectal cancer specimens was performed to study the expression
and subcellular localization of β-catenin and phosphospecific β-catenin. These results were correlated with other clinicopathological
factors and with overall survival.
Results: The majority of cancers retained some degree of β-catenin membranous staining, whereas cytoplasmic or nuclear expression
was seen in 42.5% and 20.4% of specimens, respectively. Phospho-β-catenin showed nuclear staining in 9.5% of specimens, and
there was no apparent membranous or cytoplasmic staining. There was no significant association between β-catenin or phospho-β-catenin
and grade or stage. However, there was a positive correlation between β-catenin and phospho-β-catenin ( P = 0.039), with phospho-β-catenin representing a subset of nuclear β-catenin. Patients with nuclear expression of β-catenin
did not have an altered survival compared with those that did not ( P = 0.5611). Nuclear expression of phospho-β-catenin, however, was associated with an improved survival ( P = 0.0006). In multivariate analysis, only stage and phospho-β-catenin were independently predictive of overall survival ( P < 0.001 and P = 0.0034, respectively).
Conclusions: These findings support a role for β-catenin overexpression in colorectal tumorigenesis and provide initial evidence that
phospho-β-catenin may be a marker for improved overall survival independent of stage and grade.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>PMID: 11751495</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Animals ; beta Catenin ; Biological and medical sciences ; Cadherins - analysis ; Cell Line ; Cell Nucleus - pathology ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - mortality ; Colorectal Neoplasms - pathology ; Cytoplasm - pathology ; Cytoskeletal Proteins - analysis ; Cytoskeletal Proteins - genetics ; Dogs ; Gastroenterology. Liver. Pancreas. Abdomen ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Medical sciences ; Neoplasm Staging ; Oligonucleotide Array Sequence Analysis ; Phosphoproteins - analysis ; Prognosis ; Proportional Hazards Models ; Recombinant Proteins - analysis ; Reproducibility of Results ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Survival Rate ; Trans-Activators ; Transfection ; Treatment Outcome ; Tumors</subject><ispartof>Clinical cancer research, 2001-12, Vol.7 (12), p.4013-4020</ispartof><rights>2002 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&idt=13415390$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11751495$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>CHUNG, Gina G</creatorcontrib><creatorcontrib>PROVOST, Elayne</creatorcontrib><creatorcontrib>KIELHORN, Eric P</creatorcontrib><creatorcontrib>CHARETTE, Lori A</creatorcontrib><creatorcontrib>SMITH, Bradley L</creatorcontrib><creatorcontrib>RIMM, David L</creatorcontrib><title>Tissue Microarray Analysis of β-Catenin in Colorectal Cancer Shows Nuclear Phospho-β-catenin Is Associated with a Better Prognosis</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Purpose : β-Catenin is involved in homotypic cell-cell adhesion and the wnt signaling pathway. Deregulation of β-catenin levels, caused in part by mutations of the adenomatous polyposis coli gene,
is thought to play a role in the development of colorectal and other cancers. To further elucidate their roles, the expression
pattern of β-catenin and phosphospecific β-catenin was correlated with clinical outcome in a series of patients with colorectal
cancer.
Experimental Design: Immunohistochemical analysis of a tissue microarray with 650 colorectal cancer specimens was performed to study the expression
and subcellular localization of β-catenin and phosphospecific β-catenin. These results were correlated with other clinicopathological
factors and with overall survival.
Results: The majority of cancers retained some degree of β-catenin membranous staining, whereas cytoplasmic or nuclear expression
was seen in 42.5% and 20.4% of specimens, respectively. Phospho-β-catenin showed nuclear staining in 9.5% of specimens, and
there was no apparent membranous or cytoplasmic staining. There was no significant association between β-catenin or phospho-β-catenin
and grade or stage. However, there was a positive correlation between β-catenin and phospho-β-catenin ( P = 0.039), with phospho-β-catenin representing a subset of nuclear β-catenin. Patients with nuclear expression of β-catenin
did not have an altered survival compared with those that did not ( P = 0.5611). Nuclear expression of phospho-β-catenin, however, was associated with an improved survival ( P = 0.0006). In multivariate analysis, only stage and phospho-β-catenin were independently predictive of overall survival ( P < 0.001 and P = 0.0034, respectively).
Conclusions: These findings support a role for β-catenin overexpression in colorectal tumorigenesis and provide initial evidence that
phospho-β-catenin may be a marker for improved overall survival independent of stage and grade.</description><subject>Animals</subject><subject>beta Catenin</subject><subject>Biological and medical sciences</subject><subject>Cadherins - analysis</subject><subject>Cell Line</subject><subject>Cell Nucleus - pathology</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - mortality</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Cytoplasm - pathology</subject><subject>Cytoskeletal Proteins - analysis</subject><subject>Cytoskeletal Proteins - genetics</subject><subject>Dogs</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Medical sciences</subject><subject>Neoplasm Staging</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Phosphoproteins - analysis</subject><subject>Prognosis</subject><subject>Proportional Hazards Models</subject><subject>Recombinant Proteins - analysis</subject><subject>Reproducibility of Results</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</subject><subject>Survival Rate</subject><subject>Trans-Activators</subject><subject>Transfection</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkNtKw0AQhoMotlZfQfZG8Sawx25zWYOHQtWC9TpsNptmZZutOwml9z6RD-IzudSKMDAz8P0z8B0lQyKETBkdi-M4YzlJMWd0kJwBvGNMOMH8NBkQIgXhmRgmn0sL0Bv0ZHXwKgS1Q9NWuR1YQL5G319prjrT2hbFyr3zwehOOZSrVpuAXhu_BfTca2dUQIvGw6bxaUzpQ2oGaArgtY17hba2a5BCt6brYngR_Kr18dN5clIrB-bi0EfJ2_3dMn9M5y8Ps3w6TxsqcZfyjFKuRS1KTCUnY04ySQzVouKSSl3iDHMseDXhrKrrmqiKVaUxHFOtGas4GyXXv3c3wX_0BrpibUEb51RrfA-FpGwsRYYjeHkA-3JtqmIT7FqFXfHnLQJXB0CBVq4OUYeFf45xItj-0M0v19hVs7XBFHovLhiIwnRTyILQgmPC2A8-kody</recordid><startdate>20011201</startdate><enddate>20011201</enddate><creator>CHUNG, Gina G</creator><creator>PROVOST, Elayne</creator><creator>KIELHORN, Eric P</creator><creator>CHARETTE, Lori A</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>20011201</creationdate><title>Tissue Microarray Analysis of β-Catenin in Colorectal Cancer Shows Nuclear Phospho-β-catenin Is Associated with a Better Prognosis</title><author>CHUNG, Gina G ; PROVOST, Elayne ; KIELHORN, Eric P ; CHARETTE, Lori A ; SMITH, Bradley L ; RIMM, David L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h270t-49224c5f5b02741641971e2c5d4727cb0904054d843dfff1ad3dbee402cc33d43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Animals</topic><topic>beta Catenin</topic><topic>Biological and medical sciences</topic><topic>Cadherins - analysis</topic><topic>Cell Line</topic><topic>Cell Nucleus - pathology</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - mortality</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Cytoplasm - pathology</topic><topic>Cytoskeletal Proteins - analysis</topic><topic>Cytoskeletal Proteins - genetics</topic><topic>Dogs</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Medical sciences</topic><topic>Neoplasm Staging</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Phosphoproteins - analysis</topic><topic>Prognosis</topic><topic>Proportional Hazards Models</topic><topic>Recombinant Proteins - analysis</topic><topic>Reproducibility of Results</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</topic><topic>Survival Rate</topic><topic>Trans-Activators</topic><topic>Transfection</topic><topic>Treatment Outcome</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>CHUNG, Gina G</creatorcontrib><creatorcontrib>PROVOST, Elayne</creatorcontrib><creatorcontrib>KIELHORN, Eric P</creatorcontrib><creatorcontrib>CHARETTE, Lori A</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>CHUNG, Gina G</au><au>PROVOST, Elayne</au><au>KIELHORN, Eric P</au><au>CHARETTE, Lori A</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 β-Catenin in Colorectal Cancer Shows Nuclear Phospho-β-catenin Is Associated with a Better Prognosis</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2001-12-01</date><risdate>2001</risdate><volume>7</volume><issue>12</issue><spage>4013</spage><epage>4020</epage><pages>4013-4020</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Purpose : β-Catenin is involved in homotypic cell-cell adhesion and the wnt signaling pathway. Deregulation of β-catenin levels, caused in part by mutations of the adenomatous polyposis coli gene,
is thought to play a role in the development of colorectal and other cancers. To further elucidate their roles, the expression
pattern of β-catenin and phosphospecific β-catenin was correlated with clinical outcome in a series of patients with colorectal
cancer.
Experimental Design: Immunohistochemical analysis of a tissue microarray with 650 colorectal cancer specimens was performed to study the expression
and subcellular localization of β-catenin and phosphospecific β-catenin. These results were correlated with other clinicopathological
factors and with overall survival.
Results: The majority of cancers retained some degree of β-catenin membranous staining, whereas cytoplasmic or nuclear expression
was seen in 42.5% and 20.4% of specimens, respectively. Phospho-β-catenin showed nuclear staining in 9.5% of specimens, and
there was no apparent membranous or cytoplasmic staining. There was no significant association between β-catenin or phospho-β-catenin
and grade or stage. However, there was a positive correlation between β-catenin and phospho-β-catenin ( P = 0.039), with phospho-β-catenin representing a subset of nuclear β-catenin. Patients with nuclear expression of β-catenin
did not have an altered survival compared with those that did not ( P = 0.5611). Nuclear expression of phospho-β-catenin, however, was associated with an improved survival ( P = 0.0006). In multivariate analysis, only stage and phospho-β-catenin were independently predictive of overall survival ( P < 0.001 and P = 0.0034, respectively).
Conclusions: These findings support a role for β-catenin overexpression in colorectal tumorigenesis and provide initial evidence that
phospho-β-catenin may be a marker for improved overall survival independent of stage and grade.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>11751495</pmid><tpages>8</tpages></addata></record> |
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| ispartof | Clinical cancer research, 2001-12, Vol.7 (12), p.4013-4020 |
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| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Animals beta Catenin Biological and medical sciences Cadherins - analysis Cell Line Cell Nucleus - pathology Colorectal Neoplasms - genetics Colorectal Neoplasms - mortality Colorectal Neoplasms - pathology Cytoplasm - pathology Cytoskeletal Proteins - analysis Cytoskeletal Proteins - genetics Dogs Gastroenterology. Liver. Pancreas. Abdomen Gene Expression Regulation, Neoplastic Humans Immunohistochemistry Medical sciences Neoplasm Staging Oligonucleotide Array Sequence Analysis Phosphoproteins - analysis Prognosis Proportional Hazards Models Recombinant Proteins - analysis Reproducibility of Results Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Survival Rate Trans-Activators Transfection Treatment Outcome Tumors |
| title | Tissue Microarray Analysis of β-Catenin in Colorectal Cancer Shows Nuclear Phospho-β-catenin Is Associated with a Better Prognosis |
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