Expression of the High-Affinity Fluoropyrimidine-Preferring Nucleoside Transporter hCNT1 Correlates with Decreased Disease-Free Survival in Breast Cancer
Purpose: Nucleoside and nucleobase derivatives are currently used in the treatment of a variety of solid tumors; however, the role of plasma membrane transporters as biomarkers of drug metabolism has not been fully addressed. Thus, the purpose of this study was to determine whether the concentrative...
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| Veröffentlicht in: | Oncology 2006-01, Vol.70 (3), p.238-244 |
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| creator | Gloeckner-Hofmann, Katharina Guillén-Gómez, Elena Schmidtgen, Claudia Porstmann, Romy Ziegler, Ralf Stoss, Oliver Casado, F. Javier Rüschoff, Josef Pastor-Anglada, Marçal |
| description | Purpose: Nucleoside and nucleobase derivatives are currently used in the treatment of a variety of solid tumors; however, the role of plasma membrane transporters as biomarkers of drug metabolism has not been fully addressed. Thus, the purpose of this study was to determine whether the concentrative nucleoside transporter hCNT1 is a predictive marker of therapeutic response. Methods: We studied a cohort of 90 breast cancer patients who were treated with cyclophosphamide-methotrexate-5-fluorouracil after surgery and then monitored for up to 108 months. hCNT1 and enzymes associated with nucleotide metabolism (thymidine phosphorylase, dihydropyrimidine dehydrogenase and thymidylate synthase) were assessed immunohistochemically in tissue samples. Results: Human CNT1 presence was mostly cytoplasmic, with some nuclear staining. The percentage of hCNT1-positive cells correlated positively with the expression of thymidine phosphorylase and dihydropyrimidine dehydrogenase. Nuclear staining correlated negatively with decreased disease-free survival, whereas the percentage of hCNT1-positive cells correlated positively with reduced long-term survival, with the hCNT1-positive index (>80%) being indicative of poor prognosis. A relative risk of relapse was associated with high hCNT1-positive indexes, whereas when this parameter was combined with the nodal status (positive), a high risk of relapse was found, suggesting that both parameters may reflect a poor prognosis. Conclusions: These results indicate thatthe expression of the high-affinity concentrative nucleoside transporter hCNT1 has a prognostic value in determining disease-free survival and risk of relapse in breast cancer patients undergoing surgery followed by cyclophosphamide-methotrexate-5-fluorouracil chemotherapy. |
| doi_str_mv | 10.1159/000094541 |
| format | Article |
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Javier ; Rüschoff, Josef ; Pastor-Anglada, Marçal</creator><creatorcontrib>Gloeckner-Hofmann, Katharina ; Guillén-Gómez, Elena ; Schmidtgen, Claudia ; Porstmann, Romy ; Ziegler, Ralf ; Stoss, Oliver ; Casado, F. Javier ; Rüschoff, Josef ; Pastor-Anglada, Marçal</creatorcontrib><description>Purpose: Nucleoside and nucleobase derivatives are currently used in the treatment of a variety of solid tumors; however, the role of plasma membrane transporters as biomarkers of drug metabolism has not been fully addressed. Thus, the purpose of this study was to determine whether the concentrative nucleoside transporter hCNT1 is a predictive marker of therapeutic response. Methods: We studied a cohort of 90 breast cancer patients who were treated with cyclophosphamide-methotrexate-5-fluorouracil after surgery and then monitored for up to 108 months. hCNT1 and enzymes associated with nucleotide metabolism (thymidine phosphorylase, dihydropyrimidine dehydrogenase and thymidylate synthase) were assessed immunohistochemically in tissue samples. Results: Human CNT1 presence was mostly cytoplasmic, with some nuclear staining. The percentage of hCNT1-positive cells correlated positively with the expression of thymidine phosphorylase and dihydropyrimidine dehydrogenase. Nuclear staining correlated negatively with decreased disease-free survival, whereas the percentage of hCNT1-positive cells correlated positively with reduced long-term survival, with the hCNT1-positive index (>80%) being indicative of poor prognosis. A relative risk of relapse was associated with high hCNT1-positive indexes, whereas when this parameter was combined with the nodal status (positive), a high risk of relapse was found, suggesting that both parameters may reflect a poor prognosis. Conclusions: These results indicate thatthe expression of the high-affinity concentrative nucleoside transporter hCNT1 has a prognostic value in determining disease-free survival and risk of relapse in breast cancer patients undergoing surgery followed by cyclophosphamide-methotrexate-5-fluorouracil chemotherapy.</description><identifier>ISSN: 0030-2414</identifier><identifier>EISSN: 1423-0232</identifier><identifier>DOI: 10.1159/000094541</identifier><identifier>PMID: 16837820</identifier><language>eng</language><publisher>Basel, Switzerland: Karger</publisher><subject>Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biological and medical sciences ; Biomarkers, Tumor - metabolism ; Breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - metabolism ; Breast Neoplasms - mortality ; Breast Neoplasms - pathology ; Breast Neoplasms - surgery ; Chemotherapy, Adjuvant ; Correlation analysis ; Cyclophosphamide - administration & dosage ; Disease-Free Survival ; Female ; Fluorouracil - administration & dosage ; Gene expression ; Gene Expression Regulation, Neoplastic ; Gynecology. Andrology. Obstetrics ; Humans ; Immunohistochemistry ; Laboratory Investigation ; Mammary gland diseases ; Medical sciences ; Membrane Transport Proteins - metabolism ; Methotrexate - administration & dosage ; Middle Aged ; Oncology ; Predictive Value of Tests ; Prognosis ; Survivor ; Tumors</subject><ispartof>Oncology, 2006-01, Vol.70 (3), p.238-244</ispartof><rights>2006 S. Karger AG, Basel</rights><rights>2006 INIST-CNRS</rights><rights>Copyright 2006 S. Karger AG, Basel.</rights><rights>Copyright (c) 2006 S. Karger AG, Basel</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c392t-dde4ff05f31d4c7351ff63b396ee2af83ba9a46e688dfe0d1f916d266172a6c03</citedby><cites>FETCH-LOGICAL-c392t-dde4ff05f31d4c7351ff63b396ee2af83ba9a46e688dfe0d1f916d266172a6c03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2429,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18001990$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16837820$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gloeckner-Hofmann, Katharina</creatorcontrib><creatorcontrib>Guillén-Gómez, Elena</creatorcontrib><creatorcontrib>Schmidtgen, Claudia</creatorcontrib><creatorcontrib>Porstmann, Romy</creatorcontrib><creatorcontrib>Ziegler, Ralf</creatorcontrib><creatorcontrib>Stoss, Oliver</creatorcontrib><creatorcontrib>Casado, F. Javier</creatorcontrib><creatorcontrib>Rüschoff, Josef</creatorcontrib><creatorcontrib>Pastor-Anglada, Marçal</creatorcontrib><title>Expression of the High-Affinity Fluoropyrimidine-Preferring Nucleoside Transporter hCNT1 Correlates with Decreased Disease-Free Survival in Breast Cancer</title><title>Oncology</title><addtitle>Oncology</addtitle><description>Purpose: Nucleoside and nucleobase derivatives are currently used in the treatment of a variety of solid tumors; however, the role of plasma membrane transporters as biomarkers of drug metabolism has not been fully addressed. Thus, the purpose of this study was to determine whether the concentrative nucleoside transporter hCNT1 is a predictive marker of therapeutic response. Methods: We studied a cohort of 90 breast cancer patients who were treated with cyclophosphamide-methotrexate-5-fluorouracil after surgery and then monitored for up to 108 months. hCNT1 and enzymes associated with nucleotide metabolism (thymidine phosphorylase, dihydropyrimidine dehydrogenase and thymidylate synthase) were assessed immunohistochemically in tissue samples. Results: Human CNT1 presence was mostly cytoplasmic, with some nuclear staining. The percentage of hCNT1-positive cells correlated positively with the expression of thymidine phosphorylase and dihydropyrimidine dehydrogenase. Nuclear staining correlated negatively with decreased disease-free survival, whereas the percentage of hCNT1-positive cells correlated positively with reduced long-term survival, with the hCNT1-positive index (>80%) being indicative of poor prognosis. A relative risk of relapse was associated with high hCNT1-positive indexes, whereas when this parameter was combined with the nodal status (positive), a high risk of relapse was found, suggesting that both parameters may reflect a poor prognosis. Conclusions: These results indicate thatthe expression of the high-affinity concentrative nucleoside transporter hCNT1 has a prognostic value in determining disease-free survival and risk of relapse in breast cancer patients undergoing surgery followed by cyclophosphamide-methotrexate-5-fluorouracil chemotherapy.</description><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - mortality</subject><subject>Breast Neoplasms - pathology</subject><subject>Breast Neoplasms - surgery</subject><subject>Chemotherapy, Adjuvant</subject><subject>Correlation analysis</subject><subject>Cyclophosphamide - administration & dosage</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Fluorouracil - administration & dosage</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Laboratory Investigation</subject><subject>Mammary gland diseases</subject><subject>Medical sciences</subject><subject>Membrane Transport Proteins - metabolism</subject><subject>Methotrexate - administration & dosage</subject><subject>Middle Aged</subject><subject>Oncology</subject><subject>Predictive Value of Tests</subject><subject>Prognosis</subject><subject>Survivor</subject><subject>Tumors</subject><issn>0030-2414</issn><issn>1423-0232</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpd0U9v0zAYBvAIgVg3OHBGQhYSQhwC_hc3Po5sZUjTQKKcI9d-3XqkcXidbPSj8G1x1WqT8OX14afX1vMUxStGPzJW6U80Hy0ryZ4UMya5KCkX_Gkxo1TQkksmT4rTlG6zmldSPS9OmKrFvOZ0Vvy9_DMgpBRiT6In4wbIVVhvynPvQx_GHVl0U8Q47DBsgws9lN8RPCCGfk1uJttBTMEBWaLp0xBxBCSb5mbJSBMRoTMjJHIfxg25AItgEjhyEdL-Ui4QgPyY8C7cmY6Ennzeg5E0preAL4pn3nQJXh7nWfFzcblsrsrrb1--NufXpRWaj6VzIL2nlRfMSTsXFfNeiZXQCoAbX4uV0UYqUHXtPFDHvGbKcaXYnBtlqTgr3h_2Dhh_T5DGdhuSha4zPcQptXMpldaCyyzf_idv44R9_lzLOa1zAUpn9OGALMaUclbtkKMzuGsZbfdttQ9tZfvmuHBabcE9ymM9Gbw7ApOs6XwO2Yb06GpKmdZ79_rgfhlcAz6AwzP_AKkhptI</recordid><startdate>20060101</startdate><enddate>20060101</enddate><creator>Gloeckner-Hofmann, Katharina</creator><creator>Guillén-Gómez, Elena</creator><creator>Schmidtgen, Claudia</creator><creator>Porstmann, Romy</creator><creator>Ziegler, Ralf</creator><creator>Stoss, Oliver</creator><creator>Casado, F. 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Javier ; Rüschoff, Josef ; Pastor-Anglada, Marçal</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c392t-dde4ff05f31d4c7351ff63b396ee2af83ba9a46e688dfe0d1f916d266172a6c03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - mortality</topic><topic>Breast Neoplasms - pathology</topic><topic>Breast Neoplasms - surgery</topic><topic>Chemotherapy, Adjuvant</topic><topic>Correlation analysis</topic><topic>Cyclophosphamide - administration & dosage</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Fluorouracil - administration & dosage</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Laboratory Investigation</topic><topic>Mammary gland diseases</topic><topic>Medical sciences</topic><topic>Membrane Transport Proteins - metabolism</topic><topic>Methotrexate - administration & dosage</topic><topic>Middle Aged</topic><topic>Oncology</topic><topic>Predictive Value of Tests</topic><topic>Prognosis</topic><topic>Survivor</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gloeckner-Hofmann, Katharina</creatorcontrib><creatorcontrib>Guillén-Gómez, Elena</creatorcontrib><creatorcontrib>Schmidtgen, Claudia</creatorcontrib><creatorcontrib>Porstmann, Romy</creatorcontrib><creatorcontrib>Ziegler, Ralf</creatorcontrib><creatorcontrib>Stoss, Oliver</creatorcontrib><creatorcontrib>Casado, F. Javier</creatorcontrib><creatorcontrib>Rüschoff, Josef</creatorcontrib><creatorcontrib>Pastor-Anglada, Marçal</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>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>Nucleic Acids Abstracts</collection><jtitle>Oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gloeckner-Hofmann, Katharina</au><au>Guillén-Gómez, Elena</au><au>Schmidtgen, Claudia</au><au>Porstmann, Romy</au><au>Ziegler, Ralf</au><au>Stoss, Oliver</au><au>Casado, F. Javier</au><au>Rüschoff, Josef</au><au>Pastor-Anglada, Marçal</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of the High-Affinity Fluoropyrimidine-Preferring Nucleoside Transporter hCNT1 Correlates with Decreased Disease-Free Survival in Breast Cancer</atitle><jtitle>Oncology</jtitle><addtitle>Oncology</addtitle><date>2006-01-01</date><risdate>2006</risdate><volume>70</volume><issue>3</issue><spage>238</spage><epage>244</epage><pages>238-244</pages><issn>0030-2414</issn><eissn>1423-0232</eissn><abstract>Purpose: Nucleoside and nucleobase derivatives are currently used in the treatment of a variety of solid tumors; however, the role of plasma membrane transporters as biomarkers of drug metabolism has not been fully addressed. Thus, the purpose of this study was to determine whether the concentrative nucleoside transporter hCNT1 is a predictive marker of therapeutic response. Methods: We studied a cohort of 90 breast cancer patients who were treated with cyclophosphamide-methotrexate-5-fluorouracil after surgery and then monitored for up to 108 months. hCNT1 and enzymes associated with nucleotide metabolism (thymidine phosphorylase, dihydropyrimidine dehydrogenase and thymidylate synthase) were assessed immunohistochemically in tissue samples. Results: Human CNT1 presence was mostly cytoplasmic, with some nuclear staining. The percentage of hCNT1-positive cells correlated positively with the expression of thymidine phosphorylase and dihydropyrimidine dehydrogenase. Nuclear staining correlated negatively with decreased disease-free survival, whereas the percentage of hCNT1-positive cells correlated positively with reduced long-term survival, with the hCNT1-positive index (>80%) being indicative of poor prognosis. A relative risk of relapse was associated with high hCNT1-positive indexes, whereas when this parameter was combined with the nodal status (positive), a high risk of relapse was found, suggesting that both parameters may reflect a poor prognosis. Conclusions: These results indicate thatthe expression of the high-affinity concentrative nucleoside transporter hCNT1 has a prognostic value in determining disease-free survival and risk of relapse in breast cancer patients undergoing surgery followed by cyclophosphamide-methotrexate-5-fluorouracil chemotherapy.</abstract><cop>Basel, Switzerland</cop><pub>Karger</pub><pmid>16837820</pmid><doi>10.1159/000094541</doi><tpages>7</tpages></addata></record> |
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| ispartof | Oncology, 2006-01, Vol.70 (3), p.238-244 |
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| source | MEDLINE; Karger Journals Complete |
| subjects | Adult Aged Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biological and medical sciences Biomarkers, Tumor - metabolism Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - metabolism Breast Neoplasms - mortality Breast Neoplasms - pathology Breast Neoplasms - surgery Chemotherapy, Adjuvant Correlation analysis Cyclophosphamide - administration & dosage Disease-Free Survival Female Fluorouracil - administration & dosage Gene expression Gene Expression Regulation, Neoplastic Gynecology. Andrology. Obstetrics Humans Immunohistochemistry Laboratory Investigation Mammary gland diseases Medical sciences Membrane Transport Proteins - metabolism Methotrexate - administration & dosage Middle Aged Oncology Predictive Value of Tests Prognosis Survivor Tumors |
| title | Expression of the High-Affinity Fluoropyrimidine-Preferring Nucleoside Transporter hCNT1 Correlates with Decreased Disease-Free Survival in Breast Cancer |
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