Expression profiling of colorectal carcinomas using tissue microarrays: cell cycle regulatory proteins p21, p27, and p53 as immunohistochemical prognostic markers in univariate and multivariate analysis
With the rapidly growing understanding of tumor biology, molecular staging of cancer is expected to improve prognostication. This would be particularly important for cancers amenable to adjuvant treatment, such as colorectal carcinomas. To generate data for this, the tissue microarray technique may...
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| Veröffentlicht in: | Applied immunohistochemistry & molecular morphology 2004-06, Vol.12 (2), p.111-121 |
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| creator | Prall, Friedrich Ostwald, Christiane Nizze, Horst Barten, Malte |
| description | With the rapidly growing understanding of tumor biology, molecular staging of cancer is expected to improve prognostication. This would be particularly important for cancers amenable to adjuvant treatment, such as colorectal carcinomas. To generate data for this, the tissue microarray technique may prove useful. Tissue microarrays were constructed with triplicate cores (0.6 mm diameter) from the invasive margins of a consecutive single-institution series of 184 colorectal carcinomas. Immunostaining for p53, p21, p27, Ecadherin, and beta-catenin was scored. Tumor cell proliferation was assessed by mitotic indices and Ki-67 labeling, apoptosis by quantification of apoptotic bodies. Reduced nuclear immunostaining for p21 ( |
| doi_str_mv | 10.1097/00129039-200406000-00003 |
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This would be particularly important for cancers amenable to adjuvant treatment, such as colorectal carcinomas. To generate data for this, the tissue microarray technique may prove useful. Tissue microarrays were constructed with triplicate cores (0.6 mm diameter) from the invasive margins of a consecutive single-institution series of 184 colorectal carcinomas. Immunostaining for p53, p21, p27, Ecadherin, and beta-catenin was scored. Tumor cell proliferation was assessed by mitotic indices and Ki-67 labeling, apoptosis by quantification of apoptotic bodies. Reduced nuclear immunostaining for p21 (<10%) and p27 (< or =50%) and reduced membranous expression of Ecadherin were significantly associated with a poorer clinical course by univariate analysis. beta-catenin immunostaining had no prognostic impact. Mitotic and apoptotic indices as well as Ki-67 labeling below the median were indicators of poor prognosis. Complete absence of p53 nuclear staining was a significant adverse prognostic factor. By Cox regression, p53 = 0%, p53 = 0%, in combination with p27 < or = 50%, the mitotic index and the combined mitotic and apoptotic index added prognostic information to UICC stage. The authors found that growth pattern, lymphohistiocytic response, lymphatic permeation, and venous spread, too, each was a strong prognosticator in addition to UICC stage. The results support that tissue microarrays are a useful tool for screening immunohistochemical markers for prognostic use. An immunopanel of p21, p27, and p53 could be useful for prognostication in colorectal carcinoma in addition to UICC stage.</description><identifier>ISSN: 1541-2016</identifier><identifier>DOI: 10.1097/00129039-200406000-00003</identifier><identifier>PMID: 15354735</identifier><language>eng</language><publisher>United States</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Analysis of Variance ; Biomarkers - analysis ; Cell Cycle Proteins - analysis ; Colorectal Neoplasms - chemistry ; Colorectal Neoplasms - mortality ; Colorectal Neoplasms - pathology ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclin-Dependent Kinase Inhibitor p27 ; Cyclins - analysis ; Female ; Gene Expression Profiling - methods ; Gene Expression Profiling - statistics & numerical data ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Metastasis ; Prognosis ; Risk ; Survival Analysis ; Tumor Suppressor Protein p53 - analysis ; Tumor Suppressor Proteins - analysis</subject><ispartof>Applied immunohistochemistry & molecular morphology, 2004-06, Vol.12 (2), p.111-121</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c402t-bda4647aaaa70e82faec9765e18493e8a9f0a7420b542ff97d44c0d72fc4346b3</citedby><cites>FETCH-LOGICAL-c402t-bda4647aaaa70e82faec9765e18493e8a9f0a7420b542ff97d44c0d72fc4346b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,27933,27934</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15354735$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Prall, Friedrich</creatorcontrib><creatorcontrib>Ostwald, Christiane</creatorcontrib><creatorcontrib>Nizze, Horst</creatorcontrib><creatorcontrib>Barten, Malte</creatorcontrib><title>Expression profiling of colorectal carcinomas using tissue microarrays: cell cycle regulatory proteins p21, p27, and p53 as immunohistochemical prognostic markers in univariate and multivariate analysis</title><title>Applied immunohistochemistry & molecular morphology</title><addtitle>Appl Immunohistochem Mol Morphol</addtitle><description>With the rapidly growing understanding of tumor biology, molecular staging of cancer is expected to improve prognostication. This would be particularly important for cancers amenable to adjuvant treatment, such as colorectal carcinomas. To generate data for this, the tissue microarray technique may prove useful. Tissue microarrays were constructed with triplicate cores (0.6 mm diameter) from the invasive margins of a consecutive single-institution series of 184 colorectal carcinomas. Immunostaining for p53, p21, p27, Ecadherin, and beta-catenin was scored. Tumor cell proliferation was assessed by mitotic indices and Ki-67 labeling, apoptosis by quantification of apoptotic bodies. Reduced nuclear immunostaining for p21 (<10%) and p27 (< or =50%) and reduced membranous expression of Ecadherin were significantly associated with a poorer clinical course by univariate analysis. beta-catenin immunostaining had no prognostic impact. Mitotic and apoptotic indices as well as Ki-67 labeling below the median were indicators of poor prognosis. Complete absence of p53 nuclear staining was a significant adverse prognostic factor. By Cox regression, p53 = 0%, p53 = 0%, in combination with p27 < or = 50%, the mitotic index and the combined mitotic and apoptotic index added prognostic information to UICC stage. The authors found that growth pattern, lymphohistiocytic response, lymphatic permeation, and venous spread, too, each was a strong prognosticator in addition to UICC stage. The results support that tissue microarrays are a useful tool for screening immunohistochemical markers for prognostic use. An immunopanel of p21, p27, and p53 could be useful for prognostication in colorectal carcinoma in addition to UICC stage.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Analysis of Variance</subject><subject>Biomarkers - analysis</subject><subject>Cell Cycle Proteins - analysis</subject><subject>Colorectal Neoplasms - chemistry</subject><subject>Colorectal Neoplasms - mortality</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Cyclin-Dependent Kinase Inhibitor p21</subject><subject>Cyclin-Dependent Kinase Inhibitor p27</subject><subject>Cyclins - analysis</subject><subject>Female</subject><subject>Gene Expression Profiling - methods</subject><subject>Gene Expression Profiling - statistics & numerical data</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neoplasm Metastasis</subject><subject>Prognosis</subject><subject>Risk</subject><subject>Survival Analysis</subject><subject>Tumor Suppressor Protein p53 - analysis</subject><subject>Tumor Suppressor Proteins - analysis</subject><issn>1541-2016</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNUctu1TAQzaKIlpZfqLxi1cD4kThhh6rykCqxoevI15ncGhI7eGxEfpGvwre9lFoajzQ-58yMT1UxDm859PodABc9yL4WAApaAKhLgDypznijeCnz9rR6RfQdQAip1MvqlDeyUVo2Z9Wfm99rRCIXPFtjmNzs_J6Fidkwh4g2mZlZE63zYTHEMh2ekyPKyBZnYzAxmo3eM4tzQW52RhZxn2eTQtwOkgmdJ7YKflUufcWMH9naSFbU3LJkH-4dpWDvsciVZoWx94GSs2wx8QfGAvMse_fLRGcSPvCXPKdnBTNv5OiiejGZmfD1MZ9Xdx9vvl1_rm-_fvpy_eG2tgpEqnejUa3SphwN2InJoO112yDvVC-xM_0ERisBu0aJaer1qJSFUYvJKqnanTyv3jzqllF_ZqQ0LI4O6xuPIdPQtl3TSpAF2D0CyzcRRZyGNbqy1DZwGA7eDf-8G568Gx68K9TLY4-8W3D8TzwaJ_8CThOcxg</recordid><startdate>20040601</startdate><enddate>20040601</enddate><creator>Prall, Friedrich</creator><creator>Ostwald, Christiane</creator><creator>Nizze, Horst</creator><creator>Barten, Malte</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>20040601</creationdate><title>Expression profiling of colorectal carcinomas using tissue microarrays: cell cycle regulatory proteins p21, p27, and p53 as immunohistochemical prognostic markers in univariate and multivariate analysis</title><author>Prall, Friedrich ; Ostwald, Christiane ; Nizze, Horst ; Barten, Malte</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c402t-bda4647aaaa70e82faec9765e18493e8a9f0a7420b542ff97d44c0d72fc4346b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Analysis of Variance</topic><topic>Biomarkers - analysis</topic><topic>Cell Cycle Proteins - analysis</topic><topic>Colorectal Neoplasms - chemistry</topic><topic>Colorectal Neoplasms - mortality</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Cyclin-Dependent Kinase Inhibitor p21</topic><topic>Cyclin-Dependent Kinase Inhibitor p27</topic><topic>Cyclins - analysis</topic><topic>Female</topic><topic>Gene Expression Profiling - methods</topic><topic>Gene Expression Profiling - statistics & numerical data</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neoplasm Metastasis</topic><topic>Prognosis</topic><topic>Risk</topic><topic>Survival Analysis</topic><topic>Tumor Suppressor Protein p53 - analysis</topic><topic>Tumor Suppressor Proteins - analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Prall, Friedrich</creatorcontrib><creatorcontrib>Ostwald, Christiane</creatorcontrib><creatorcontrib>Nizze, Horst</creatorcontrib><creatorcontrib>Barten, Malte</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>Prall, Friedrich</au><au>Ostwald, Christiane</au><au>Nizze, Horst</au><au>Barten, Malte</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression profiling of colorectal carcinomas using tissue microarrays: cell cycle regulatory proteins p21, p27, and p53 as immunohistochemical prognostic markers in univariate and multivariate analysis</atitle><jtitle>Applied immunohistochemistry & molecular morphology</jtitle><addtitle>Appl Immunohistochem Mol Morphol</addtitle><date>2004-06-01</date><risdate>2004</risdate><volume>12</volume><issue>2</issue><spage>111</spage><epage>121</epage><pages>111-121</pages><issn>1541-2016</issn><abstract>With the rapidly growing understanding of tumor biology, molecular staging of cancer is expected to improve prognostication. This would be particularly important for cancers amenable to adjuvant treatment, such as colorectal carcinomas. To generate data for this, the tissue microarray technique may prove useful. Tissue microarrays were constructed with triplicate cores (0.6 mm diameter) from the invasive margins of a consecutive single-institution series of 184 colorectal carcinomas. Immunostaining for p53, p21, p27, Ecadherin, and beta-catenin was scored. Tumor cell proliferation was assessed by mitotic indices and Ki-67 labeling, apoptosis by quantification of apoptotic bodies. Reduced nuclear immunostaining for p21 (<10%) and p27 (< or =50%) and reduced membranous expression of Ecadherin were significantly associated with a poorer clinical course by univariate analysis. beta-catenin immunostaining had no prognostic impact. Mitotic and apoptotic indices as well as Ki-67 labeling below the median were indicators of poor prognosis. Complete absence of p53 nuclear staining was a significant adverse prognostic factor. By Cox regression, p53 = 0%, p53 = 0%, in combination with p27 < or = 50%, the mitotic index and the combined mitotic and apoptotic index added prognostic information to UICC stage. The authors found that growth pattern, lymphohistiocytic response, lymphatic permeation, and venous spread, too, each was a strong prognosticator in addition to UICC stage. The results support that tissue microarrays are a useful tool for screening immunohistochemical markers for prognostic use. An immunopanel of p21, p27, and p53 could be useful for prognostication in colorectal carcinoma in addition to UICC stage.</abstract><cop>United States</cop><pmid>15354735</pmid><doi>10.1097/00129039-200406000-00003</doi><tpages>11</tpages></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Analysis of Variance Biomarkers - analysis Cell Cycle Proteins - analysis Colorectal Neoplasms - chemistry Colorectal Neoplasms - mortality Colorectal Neoplasms - pathology Cyclin-Dependent Kinase Inhibitor p21 Cyclin-Dependent Kinase Inhibitor p27 Cyclins - analysis Female Gene Expression Profiling - methods Gene Expression Profiling - statistics & numerical data Humans Immunohistochemistry Male Middle Aged Neoplasm Metastasis Prognosis Risk Survival Analysis Tumor Suppressor Protein p53 - analysis Tumor Suppressor Proteins - analysis |
| title | Expression profiling of colorectal carcinomas using tissue microarrays: cell cycle regulatory proteins p21, p27, and p53 as immunohistochemical prognostic markers in univariate and multivariate analysis |
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