Proteomic Strategies to Reveal Tumor Heterogeneity among Urothelial Papillomas
Proteomics and immunohistochemistry were used to reveal tumor heterogeneity among urothelial papillomas (UPs) with the long term goal of predicting their biological potential in terms of outcome. First, we identified proteins that were deregulated in invasive fresh lesions as compared with normal ur...
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| Veröffentlicht in: | Molecular & cellular proteomics 2002-04, Vol.1 (4), p.269-279 |
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| creator | Celis, Julio E Celis, Pamela Palsdottir, Hildur Østergaard, Morten Gromov, Pavel Primdahl, Hanne Ørntoft, Torben F Wolf, Hans Celis, Ariana Gromova, Irina |
| description | Proteomics and immunohistochemistry were used to reveal tumor heterogeneity among urothelial papillomas (UPs) with the long
term goal of predicting their biological potential in terms of outcome. First, we identified proteins that were deregulated
in invasive fresh lesions as compared with normal urothelium, and thereafter we immunostained UPs with a panel of antibodies
against some of the markers. Twenty-two major proteins showing variations of 2-fold or more in at least one-third of the invasive
lesions were selected. Specific antibodies against several of the proteins were obtained, but only a few reacted positively
in immunostaining. A panel consisting of antibodies against keratinocytes (CKs) 5, 13, 18, and 20 and markers of squamous
metaplasia (CKs 7, 8, and 14) was used to probe normal urothelium and 30 UPs collected during a period of five years. Four
UPs showed a normal phenotype, whereas the rest could be grouped in five major types that shared aberrant staining with the
CK20 antibody. Type 1 heterogeneity ( n = 4) showed preferred staining of the umbrella cells with the CK8 antibody. Type 2 ( n = 11) was typified by the staining of the basal and intermediate layers with the CK20 antibody. Type 3 ( n = 7) was characterized by the predominant staining of the basal cell layer with the CK5 antibody. Type 4 ( n = 1) showed areas of CK7 negative cells, whereas type 5 ( n = 3) showed loss of staining of the basal cells with the CK20. 29% of the patients experienced recurrences, but none progressed
to invasive disease. Patients harboring phenotypic alterations in the basal cell compartment (types 3 and 5) showed the highest
number of recurrences (4/7 and 2/3, respectively), and all type 3 lesions progressed to a higher degree of dedifferentiation . Even though a long term prospective study involving a larger sample size is required to assess the biological potential of
these lesions, we believe that this approach will prove instrumental for revealing early phenotypic changes in different types
of cancer. |
| doi_str_mv | 10.1074/mcp.M100031-MCP200 |
| format | Article |
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term goal of predicting their biological potential in terms of outcome. First, we identified proteins that were deregulated
in invasive fresh lesions as compared with normal urothelium, and thereafter we immunostained UPs with a panel of antibodies
against some of the markers. Twenty-two major proteins showing variations of 2-fold or more in at least one-third of the invasive
lesions were selected. Specific antibodies against several of the proteins were obtained, but only a few reacted positively
in immunostaining. A panel consisting of antibodies against keratinocytes (CKs) 5, 13, 18, and 20 and markers of squamous
metaplasia (CKs 7, 8, and 14) was used to probe normal urothelium and 30 UPs collected during a period of five years. Four
UPs showed a normal phenotype, whereas the rest could be grouped in five major types that shared aberrant staining with the
CK20 antibody. Type 1 heterogeneity ( n = 4) showed preferred staining of the umbrella cells with the CK8 antibody. Type 2 ( n = 11) was typified by the staining of the basal and intermediate layers with the CK20 antibody. Type 3 ( n = 7) was characterized by the predominant staining of the basal cell layer with the CK5 antibody. Type 4 ( n = 1) showed areas of CK7 negative cells, whereas type 5 ( n = 3) showed loss of staining of the basal cells with the CK20. 29% of the patients experienced recurrences, but none progressed
to invasive disease. Patients harboring phenotypic alterations in the basal cell compartment (types 3 and 5) showed the highest
number of recurrences (4/7 and 2/3, respectively), and all type 3 lesions progressed to a higher degree of dedifferentiation . Even though a long term prospective study involving a larger sample size is required to assess the biological potential of
these lesions, we believe that this approach will prove instrumental for revealing early phenotypic changes in different types
of cancer.</description><identifier>ISSN: 1535-9476</identifier><identifier>EISSN: 1535-9484</identifier><identifier>DOI: 10.1074/mcp.M100031-MCP200</identifier><identifier>PMID: 12096109</identifier><language>eng</language><publisher>United States: American Society for Biochemistry and Molecular Biology</publisher><subject>Antibodies - metabolism ; Biomarkers, Tumor - metabolism ; Biopsy ; Blotting, Western ; Calgranulin B - biosynthesis ; Down-Regulation ; Electrophoresis, Gel, Two-Dimensional ; Fluorescent Antibody Technique, Indirect ; Heat-Shock Proteins - biosynthesis ; HSP30 Heat-Shock Proteins ; Humans ; Mass Spectrometry ; Membrane Proteins - biosynthesis ; Neoplasm Invasiveness ; Papilloma - diagnosis ; Papilloma - metabolism ; Phenotype ; Recurrence ; Time Factors ; Up-Regulation ; Urinary Bladder Neoplasms - diagnosis ; Urinary Bladder Neoplasms - metabolism ; Urothelium - metabolism ; Urothelium - pathology</subject><ispartof>Molecular & cellular proteomics, 2002-04, Vol.1 (4), p.269-279</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c367t-4760e7fed16dd6c8a995cf0ca50edbc07be0d77d731861c8835b801e87fc48433</citedby><cites>FETCH-LOGICAL-c367t-4760e7fed16dd6c8a995cf0ca50edbc07be0d77d731861c8835b801e87fc48433</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12096109$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Celis, Julio E</creatorcontrib><creatorcontrib>Celis, Pamela</creatorcontrib><creatorcontrib>Palsdottir, Hildur</creatorcontrib><creatorcontrib>Østergaard, Morten</creatorcontrib><creatorcontrib>Gromov, Pavel</creatorcontrib><creatorcontrib>Primdahl, Hanne</creatorcontrib><creatorcontrib>Ørntoft, Torben F</creatorcontrib><creatorcontrib>Wolf, Hans</creatorcontrib><creatorcontrib>Celis, Ariana</creatorcontrib><creatorcontrib>Gromova, Irina</creatorcontrib><title>Proteomic Strategies to Reveal Tumor Heterogeneity among Urothelial Papillomas</title><title>Molecular & cellular proteomics</title><addtitle>Mol Cell Proteomics</addtitle><description>Proteomics and immunohistochemistry were used to reveal tumor heterogeneity among urothelial papillomas (UPs) with the long
term goal of predicting their biological potential in terms of outcome. First, we identified proteins that were deregulated
in invasive fresh lesions as compared with normal urothelium, and thereafter we immunostained UPs with a panel of antibodies
against some of the markers. Twenty-two major proteins showing variations of 2-fold or more in at least one-third of the invasive
lesions were selected. Specific antibodies against several of the proteins were obtained, but only a few reacted positively
in immunostaining. A panel consisting of antibodies against keratinocytes (CKs) 5, 13, 18, and 20 and markers of squamous
metaplasia (CKs 7, 8, and 14) was used to probe normal urothelium and 30 UPs collected during a period of five years. Four
UPs showed a normal phenotype, whereas the rest could be grouped in five major types that shared aberrant staining with the
CK20 antibody. Type 1 heterogeneity ( n = 4) showed preferred staining of the umbrella cells with the CK8 antibody. Type 2 ( n = 11) was typified by the staining of the basal and intermediate layers with the CK20 antibody. Type 3 ( n = 7) was characterized by the predominant staining of the basal cell layer with the CK5 antibody. Type 4 ( n = 1) showed areas of CK7 negative cells, whereas type 5 ( n = 3) showed loss of staining of the basal cells with the CK20. 29% of the patients experienced recurrences, but none progressed
to invasive disease. Patients harboring phenotypic alterations in the basal cell compartment (types 3 and 5) showed the highest
number of recurrences (4/7 and 2/3, respectively), and all type 3 lesions progressed to a higher degree of dedifferentiation . Even though a long term prospective study involving a larger sample size is required to assess the biological potential of
these lesions, we believe that this approach will prove instrumental for revealing early phenotypic changes in different types
of cancer.</description><subject>Antibodies - metabolism</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Biopsy</subject><subject>Blotting, Western</subject><subject>Calgranulin B - biosynthesis</subject><subject>Down-Regulation</subject><subject>Electrophoresis, Gel, Two-Dimensional</subject><subject>Fluorescent Antibody Technique, Indirect</subject><subject>Heat-Shock Proteins - biosynthesis</subject><subject>HSP30 Heat-Shock Proteins</subject><subject>Humans</subject><subject>Mass Spectrometry</subject><subject>Membrane Proteins - biosynthesis</subject><subject>Neoplasm Invasiveness</subject><subject>Papilloma - diagnosis</subject><subject>Papilloma - metabolism</subject><subject>Phenotype</subject><subject>Recurrence</subject><subject>Time Factors</subject><subject>Up-Regulation</subject><subject>Urinary Bladder Neoplasms - diagnosis</subject><subject>Urinary Bladder Neoplasms - metabolism</subject><subject>Urothelium - metabolism</subject><subject>Urothelium - pathology</subject><issn>1535-9476</issn><issn>1535-9484</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkMtOwzAQRS0EoqXwAywgK3Yp47ycLFEFFIlCBe3acpxJahTXxU5A_XuMUsFqZnHu1cwh5JLClAJLbrXcTRcUAGIaLmbLCOCIjGkap2GR5Mnx386yETlz7gMgAsrSUzKiERQZhWJMXpbWdGi0ksF7Z0WHjUIXdCZ4wy8UbbDqtbHBHDu0psEtqm4fCG22TbD2wQ22ykNLsVNta7Rw5-SkFq3Di8OckPXD_Wo2D59fH59md8-hjDPWhf4kQFZjRbOqymQuiiKVNUiRAlalBFYiVIxVLKZ5RmWex2mZA8Wc1dK_FscTcjP07qz57NF1XCsnsW3FFk3vOKO555PMg9EASmucs1jznVVa2D2nwH8tcm-RHyzywaIPXR3a-1Jj9R85aPPA9QBsVLP5VhZ5qYzcoOaUJzzKivgHkvh6IA</recordid><startdate>20020401</startdate><enddate>20020401</enddate><creator>Celis, Julio E</creator><creator>Celis, Pamela</creator><creator>Palsdottir, Hildur</creator><creator>Østergaard, Morten</creator><creator>Gromov, Pavel</creator><creator>Primdahl, Hanne</creator><creator>Ørntoft, Torben F</creator><creator>Wolf, Hans</creator><creator>Celis, Ariana</creator><creator>Gromova, Irina</creator><general>American Society for Biochemistry and Molecular Biology</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>20020401</creationdate><title>Proteomic Strategies to Reveal Tumor Heterogeneity among Urothelial Papillomas</title><author>Celis, Julio E ; Celis, Pamela ; Palsdottir, Hildur ; Østergaard, Morten ; Gromov, Pavel ; Primdahl, Hanne ; Ørntoft, Torben F ; Wolf, Hans ; Celis, Ariana ; Gromova, Irina</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c367t-4760e7fed16dd6c8a995cf0ca50edbc07be0d77d731861c8835b801e87fc48433</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Antibodies - metabolism</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Biopsy</topic><topic>Blotting, Western</topic><topic>Calgranulin B - biosynthesis</topic><topic>Down-Regulation</topic><topic>Electrophoresis, Gel, Two-Dimensional</topic><topic>Fluorescent Antibody Technique, Indirect</topic><topic>Heat-Shock Proteins - biosynthesis</topic><topic>HSP30 Heat-Shock Proteins</topic><topic>Humans</topic><topic>Mass Spectrometry</topic><topic>Membrane Proteins - biosynthesis</topic><topic>Neoplasm Invasiveness</topic><topic>Papilloma - diagnosis</topic><topic>Papilloma - metabolism</topic><topic>Phenotype</topic><topic>Recurrence</topic><topic>Time Factors</topic><topic>Up-Regulation</topic><topic>Urinary Bladder Neoplasms - diagnosis</topic><topic>Urinary Bladder Neoplasms - metabolism</topic><topic>Urothelium - metabolism</topic><topic>Urothelium - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Celis, Julio E</creatorcontrib><creatorcontrib>Celis, Pamela</creatorcontrib><creatorcontrib>Palsdottir, Hildur</creatorcontrib><creatorcontrib>Østergaard, Morten</creatorcontrib><creatorcontrib>Gromov, Pavel</creatorcontrib><creatorcontrib>Primdahl, Hanne</creatorcontrib><creatorcontrib>Ørntoft, Torben F</creatorcontrib><creatorcontrib>Wolf, Hans</creatorcontrib><creatorcontrib>Celis, Ariana</creatorcontrib><creatorcontrib>Gromova, Irina</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>Molecular & cellular proteomics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Celis, Julio E</au><au>Celis, Pamela</au><au>Palsdottir, Hildur</au><au>Østergaard, Morten</au><au>Gromov, Pavel</au><au>Primdahl, Hanne</au><au>Ørntoft, Torben F</au><au>Wolf, Hans</au><au>Celis, Ariana</au><au>Gromova, Irina</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Proteomic Strategies to Reveal Tumor Heterogeneity among Urothelial Papillomas</atitle><jtitle>Molecular & cellular proteomics</jtitle><addtitle>Mol Cell Proteomics</addtitle><date>2002-04-01</date><risdate>2002</risdate><volume>1</volume><issue>4</issue><spage>269</spage><epage>279</epage><pages>269-279</pages><issn>1535-9476</issn><eissn>1535-9484</eissn><abstract>Proteomics and immunohistochemistry were used to reveal tumor heterogeneity among urothelial papillomas (UPs) with the long
term goal of predicting their biological potential in terms of outcome. First, we identified proteins that were deregulated
in invasive fresh lesions as compared with normal urothelium, and thereafter we immunostained UPs with a panel of antibodies
against some of the markers. Twenty-two major proteins showing variations of 2-fold or more in at least one-third of the invasive
lesions were selected. Specific antibodies against several of the proteins were obtained, but only a few reacted positively
in immunostaining. A panel consisting of antibodies against keratinocytes (CKs) 5, 13, 18, and 20 and markers of squamous
metaplasia (CKs 7, 8, and 14) was used to probe normal urothelium and 30 UPs collected during a period of five years. Four
UPs showed a normal phenotype, whereas the rest could be grouped in five major types that shared aberrant staining with the
CK20 antibody. Type 1 heterogeneity ( n = 4) showed preferred staining of the umbrella cells with the CK8 antibody. Type 2 ( n = 11) was typified by the staining of the basal and intermediate layers with the CK20 antibody. Type 3 ( n = 7) was characterized by the predominant staining of the basal cell layer with the CK5 antibody. Type 4 ( n = 1) showed areas of CK7 negative cells, whereas type 5 ( n = 3) showed loss of staining of the basal cells with the CK20. 29% of the patients experienced recurrences, but none progressed
to invasive disease. Patients harboring phenotypic alterations in the basal cell compartment (types 3 and 5) showed the highest
number of recurrences (4/7 and 2/3, respectively), and all type 3 lesions progressed to a higher degree of dedifferentiation . Even though a long term prospective study involving a larger sample size is required to assess the biological potential of
these lesions, we believe that this approach will prove instrumental for revealing early phenotypic changes in different types
of cancer.</abstract><cop>United States</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>12096109</pmid><doi>10.1074/mcp.M100031-MCP200</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Antibodies - metabolism Biomarkers, Tumor - metabolism Biopsy Blotting, Western Calgranulin B - biosynthesis Down-Regulation Electrophoresis, Gel, Two-Dimensional Fluorescent Antibody Technique, Indirect Heat-Shock Proteins - biosynthesis HSP30 Heat-Shock Proteins Humans Mass Spectrometry Membrane Proteins - biosynthesis Neoplasm Invasiveness Papilloma - diagnosis Papilloma - metabolism Phenotype Recurrence Time Factors Up-Regulation Urinary Bladder Neoplasms - diagnosis Urinary Bladder Neoplasms - metabolism Urothelium - metabolism Urothelium - pathology |
| title | Proteomic Strategies to Reveal Tumor Heterogeneity among Urothelial Papillomas |
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