Expression of DNA damage response proteins and complete remission after radiotherapy of stage IB-IIA of cervical cancer
The primary aim of this study was to investigate if the expression of the DNA damage identifying protein DNA-PKcs known to be involved in DNA repair after treatment with ionising radiation can be used as a predictive marker for radiotherapy (RT) response in cervical cancer. Formalin-fixed primary tu...
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creator | Beskow, C Kanter, L Holgersson, Å Nilsson, B Frankendal, B Åvall-Lundqvist, E Lewensohn, R |
description | The primary aim of this study was to investigate if the expression of the DNA damage identifying protein DNA-PKcs known to be involved in DNA repair after treatment with ionising radiation can be used as a predictive marker for radiotherapy (RT) response in cervical cancer. Formalin-fixed primary tumour biopsies from 109 patients with cervical cancer, FIGO-stage IB–IIA, treated with preoperative brachytherapy followed by radical surgery were analysed by immunohistochemistry. In addition, correlation studies between early pathological tumour response to radiation and expression of Ku86, Ku70, Mdm-2, p53 and p21 in primary tumours were also performed. We found that tumour-transformed tissue shows positive immunostaining of DNA-PKcs, Ku86 and Ku70, while non-neoplastic squamous epithelium and tumour-free cervix glands show negative immunoreactivity. Expression of DNA-PKcs positively correlated with both Ku86 and Ku70, and a statistically significant correlation between the Ku subunits was also found. After RT, 85 patients demonstrated pathologic complete remission (pCR), whereas 24 patients had residual tumour in the surgical specimen (non-pCR). The main finding of our study is that there was no correlation between the outcome of RT and the expression of DNA-PK subunits. Positive p53 tumours were significantly more common among non-pCR cases than in patients with pCR (
P
=0.031). Expression of p21 and Mdm-2 did not correlate with the outcome of RT. |
doi_str_mv | 10.1038/sj.bjc.6603153 |
format | Article |
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P
=0.031). Expression of p21 and Mdm-2 did not correlate with the outcome of RT.</description><identifier>ISSN: 0007-0920</identifier><identifier>ISSN: 1532-1827</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/sj.bjc.6603153</identifier><identifier>PMID: 16685270</identifier><identifier>CODEN: BJCAAI</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Cervical cancer ; DNA Damage ; DNA Repair - genetics ; DNA, Neoplasm - genetics ; Drug Resistance ; Epidemiology ; Female ; Female genital diseases ; Gynecology. Andrology. Obstetrics ; Humans ; Immunohistochemistry ; Medical sciences ; Medicin och hälsovetenskap ; Molecular Diagnostics ; Molecular Medicine ; Neoplasm Proteins - genetics ; Neoplasm Staging ; Oncology ; Treatment Outcome ; Tumors ; Uterine Cervical Neoplasms - genetics ; Uterine Cervical Neoplasms - pathology ; Uterine Cervical Neoplasms - radiotherapy</subject><ispartof>British journal of cancer, 2006-06, Vol.94 (11), p.1683-1689</ispartof><rights>The Author(s) 2006</rights><rights>2006 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Jun 5, 2006</rights><rights>Copyright © 2006 Cancer Research UK 2006 Cancer Research UK</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c729t-5f584ba3628507341f074afb7da9573c179d47814d52cf01cb19bf305471a513</citedby><cites>FETCH-LOGICAL-c729t-5f584ba3628507341f074afb7da9573c179d47814d52cf01cb19bf305471a513</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361310/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361310/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,552,727,780,784,885,2727,27924,27925,41488,42557,51319,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17859860$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16685270$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-133694$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:1932565$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Beskow, C</creatorcontrib><creatorcontrib>Kanter, L</creatorcontrib><creatorcontrib>Holgersson, Å</creatorcontrib><creatorcontrib>Nilsson, B</creatorcontrib><creatorcontrib>Frankendal, B</creatorcontrib><creatorcontrib>Åvall-Lundqvist, E</creatorcontrib><creatorcontrib>Lewensohn, R</creatorcontrib><title>Expression of DNA damage response proteins and complete remission after radiotherapy of stage IB-IIA of cervical cancer</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>The primary aim of this study was to investigate if the expression of the DNA damage identifying protein DNA-PKcs known to be involved in DNA repair after treatment with ionising radiation can be used as a predictive marker for radiotherapy (RT) response in cervical cancer. Formalin-fixed primary tumour biopsies from 109 patients with cervical cancer, FIGO-stage IB–IIA, treated with preoperative brachytherapy followed by radical surgery were analysed by immunohistochemistry. In addition, correlation studies between early pathological tumour response to radiation and expression of Ku86, Ku70, Mdm-2, p53 and p21 in primary tumours were also performed. We found that tumour-transformed tissue shows positive immunostaining of DNA-PKcs, Ku86 and Ku70, while non-neoplastic squamous epithelium and tumour-free cervix glands show negative immunoreactivity. Expression of DNA-PKcs positively correlated with both Ku86 and Ku70, and a statistically significant correlation between the Ku subunits was also found. After RT, 85 patients demonstrated pathologic complete remission (pCR), whereas 24 patients had residual tumour in the surgical specimen (non-pCR). The main finding of our study is that there was no correlation between the outcome of RT and the expression of DNA-PK subunits. Positive p53 tumours were significantly more common among non-pCR cases than in patients with pCR (
P
=0.031). Expression of p21 and Mdm-2 did not correlate with the outcome of RT.</description><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Cervical cancer</subject><subject>DNA Damage</subject><subject>DNA Repair - genetics</subject><subject>DNA, Neoplasm - genetics</subject><subject>Drug Resistance</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Female genital diseases</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Medical sciences</subject><subject>Medicin och hälsovetenskap</subject><subject>Molecular Diagnostics</subject><subject>Molecular Medicine</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Staging</subject><subject>Oncology</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><subject>Uterine Cervical Neoplasms - genetics</subject><subject>Uterine Cervical Neoplasms - pathology</subject><subject>Uterine Cervical Neoplasms - radiotherapy</subject><issn>0007-0920</issn><issn>1532-1827</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>D8T</sourceid><recordid>eNp9kstv1DAQhy0EosvClRsoQgJO2foRP3JBWtoCK1VwqbhajuNsvWTtYCct_e9xlLRLkdqLX_PNjGfmB8BrBFcIEnEcd6tqp1eMQYIoeQIWacU5Epg_BQsIIc9hieEReBHjLl1LKPhzcIQYExRzuADXZ3-6YGK03mW-yU6_r7Na7dXWZOm18y6arAu-N9bFTLk6037ftaYfzXs7uammNyELqra-vzRBdTdjpNiPQTaf881mPd61CVdWqzbTyqXzS_CsUW00r-Z9CS6-nF2cfMvPf3zdnKzPc81x2ee0oaKoFGFYUMhJgRrIC9VUvFYl5UQjXtYFF6ioKdYNRLpCZdUQSAuOFEVkCfIpbLw23VDJLti9CjfSKyvnp1_pZCTllEOReP4gn_pQH5xuHVFJMGX00Uyn9uda-rCVrR0kIoSVReI_TXyC96bWxvVBtfcT3rM4eym3_kpiwhBJs1-Cj3OA4H8PJvYyDUSbtlXO-CFKzjDmGOGxCR8eJZmAmOFUyBK8-w_c-SG4NJ-UNamHTYWuJkgHH2Mwzd2fEZSjJmXcyaRJOWsyObz9t9IDPoswAe9nQMWkkCYkhdh44LigpWAjdzy3OJnc1oTD9x5M_WbycKofgrkLeWv_C4IyBis</recordid><startdate>20060605</startdate><enddate>20060605</enddate><creator>Beskow, C</creator><creator>Kanter, L</creator><creator>Holgersson, Å</creator><creator>Nilsson, B</creator><creator>Frankendal, B</creator><creator>Åvall-Lundqvist, E</creator><creator>Lewensohn, R</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>IQODW</scope><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>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7TM</scope><scope>7U7</scope><scope>C1K</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>DG8</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>20060605</creationdate><title>Expression of DNA damage response proteins and complete remission after radiotherapy of stage IB-IIA of cervical cancer</title><author>Beskow, C ; Kanter, L ; Holgersson, Å ; Nilsson, B ; Frankendal, B ; Åvall-Lundqvist, E ; Lewensohn, R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c729t-5f584ba3628507341f074afb7da9573c179d47814d52cf01cb19bf305471a513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Cervical cancer</topic><topic>DNA Damage</topic><topic>DNA Repair - genetics</topic><topic>DNA, Neoplasm - genetics</topic><topic>Drug Resistance</topic><topic>Epidemiology</topic><topic>Female</topic><topic>Female genital diseases</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Medical sciences</topic><topic>Medicin och hälsovetenskap</topic><topic>Molecular Diagnostics</topic><topic>Molecular Medicine</topic><topic>Neoplasm Proteins - genetics</topic><topic>Neoplasm Staging</topic><topic>Oncology</topic><topic>Treatment Outcome</topic><topic>Tumors</topic><topic>Uterine Cervical Neoplasms - genetics</topic><topic>Uterine Cervical Neoplasms - pathology</topic><topic>Uterine Cervical Neoplasms - radiotherapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Beskow, C</creatorcontrib><creatorcontrib>Kanter, L</creatorcontrib><creatorcontrib>Holgersson, Å</creatorcontrib><creatorcontrib>Nilsson, B</creatorcontrib><creatorcontrib>Frankendal, B</creatorcontrib><creatorcontrib>Åvall-Lundqvist, E</creatorcontrib><creatorcontrib>Lewensohn, R</creatorcontrib><collection>Springer Nature OA Free Journals</collection><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>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS 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>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</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 China</collection><collection>MEDLINE - Academic</collection><collection>Nucleic Acids Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Linköpings universitet</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Beskow, C</au><au>Kanter, L</au><au>Holgersson, Å</au><au>Nilsson, B</au><au>Frankendal, B</au><au>Åvall-Lundqvist, E</au><au>Lewensohn, R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of DNA damage response proteins and complete remission after radiotherapy of stage IB-IIA of cervical cancer</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2006-06-05</date><risdate>2006</risdate><volume>94</volume><issue>11</issue><spage>1683</spage><epage>1689</epage><pages>1683-1689</pages><issn>0007-0920</issn><issn>1532-1827</issn><eissn>1532-1827</eissn><coden>BJCAAI</coden><abstract>The primary aim of this study was to investigate if the expression of the DNA damage identifying protein DNA-PKcs known to be involved in DNA repair after treatment with ionising radiation can be used as a predictive marker for radiotherapy (RT) response in cervical cancer. Formalin-fixed primary tumour biopsies from 109 patients with cervical cancer, FIGO-stage IB–IIA, treated with preoperative brachytherapy followed by radical surgery were analysed by immunohistochemistry. In addition, correlation studies between early pathological tumour response to radiation and expression of Ku86, Ku70, Mdm-2, p53 and p21 in primary tumours were also performed. We found that tumour-transformed tissue shows positive immunostaining of DNA-PKcs, Ku86 and Ku70, while non-neoplastic squamous epithelium and tumour-free cervix glands show negative immunoreactivity. Expression of DNA-PKcs positively correlated with both Ku86 and Ku70, and a statistically significant correlation between the Ku subunits was also found. After RT, 85 patients demonstrated pathologic complete remission (pCR), whereas 24 patients had residual tumour in the surgical specimen (non-pCR). The main finding of our study is that there was no correlation between the outcome of RT and the expression of DNA-PK subunits. Positive p53 tumours were significantly more common among non-pCR cases than in patients with pCR (
P
=0.031). Expression of p21 and Mdm-2 did not correlate with the outcome of RT.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>16685270</pmid><doi>10.1038/sj.bjc.6603153</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Biological and medical sciences Biomedical and Life Sciences Biomedicine Cancer Research Cervical cancer DNA Damage DNA Repair - genetics DNA, Neoplasm - genetics Drug Resistance Epidemiology Female Female genital diseases Gynecology. Andrology. Obstetrics Humans Immunohistochemistry Medical sciences Medicin och hälsovetenskap Molecular Diagnostics Molecular Medicine Neoplasm Proteins - genetics Neoplasm Staging Oncology Treatment Outcome Tumors Uterine Cervical Neoplasms - genetics Uterine Cervical Neoplasms - pathology Uterine Cervical Neoplasms - radiotherapy |
title | Expression of DNA damage response proteins and complete remission after radiotherapy of stage IB-IIA of cervical cancer |
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