Epidermal growth factor receptor (EGFR) and prostaglandin-endoperoxide synthase 2 (PTGS2) are prognostic biomarkers for patients with resected colorectal cancer liver metastases
Background: Resection of colorectal cancer liver metastasis (CRCLM) with curative intent has long-term benefit in ∼40% of cases. Prognostic biomarkers are needed to improve clinical management and reduce futile surgeries. Expression of epidermal growth factor receptor (EGFR) and prostaglandin-endope...
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| Veröffentlicht in: | British journal of cancer 2014-08, Vol.111 (4), p.749-755 |
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| creator | Goos, J A C M Hiemstra, A C Coupé, V M H Diosdado, B Kooijman, W Delis-Van Diemen, P M Karga, C Beliën, J A M Menke-van der Houven van Oordt, C W Geldof, A A Meijer, G A Hoekstra, O S Fijneman, R J A |
| description | Background:
Resection of colorectal cancer liver metastasis (CRCLM) with curative intent has long-term benefit in ∼40% of cases. Prognostic biomarkers are needed to improve clinical management and reduce futile surgeries. Expression of epidermal growth factor receptor (EGFR) and prostaglandin-endoperoxide synthase 2 (PTGS2; also known as cyclooxygenase-2) has been associated with carcinogenesis and survival. We investigated the prognostic value of EGFR and PTGS2 expression in patients with resected CRCLM.
Methods:
Formalin-fixed paraffin-embedded CRCLM tissue and corresponding primary tumour specimens from a multi-institutional cohort of patients who underwent liver resection between 1990 and 2010 were incorporated into tissue microarrays (TMAs). TMAs were stained for EGFR and PTGS2 by immunohistochemistry. The hazard rate ratio (HRR) for the association between expression in CRCLM and overall survival was calculated using a 500-fold cross-validation procedure.
Results:
EGFR and PTGS2 expression could be evaluated in 323 and 351 patients, respectively. EGFR expression in CRCLM was associated with poor prognosis (HRR 1.54;
P |
| doi_str_mv | 10.1038/bjc.2014.354 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4134500</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3402049801</sourcerecordid><originalsourceid>FETCH-LOGICAL-c550t-47f057841bd1ac46a3a8f68006208e78447ffd24ec4013277a7986df80cab1b23</originalsourceid><addsrcrecordid>eNptkVGL1DAUhYMo7rj65rMERFjBjkmaTNMXQZbZUVhQdH0OaXrbydhpapLZdX-W_9A7zLiu4Eubcr97zmkOIc85m3NW6rfNxs0F43JeKvmAzLgqRcG1qB6SGWOsKlgt2Al5ktIGP2umq8fkRMhal2UlZuTXcvItxK0daB_DTV7TzrocIo3gYNofzpariy-vqR1bOsWQsu0HPPuxgLENE8TwEwVouh3z2iaggp59vlp9FbgRYb_Rj7jkHW182Nr4HWKiHcpONnsYc6I3Hk0jJHAZWurCENA6Yx5nRweRDv4an1vIFr0TpKfkUWeHBM-O71Py7WJ5df6huPy0-nj-_rJwSrFcyKpjqtKSNy23Ti5saXW30IwtBNOAAwS6VkhwkvFSVJWtar1oO82cbXgjylPy7qA77ZottA7DRjuYKXr8jVsTrDf_Tka_Nn24NpKXUjGGAi-PAjH82EHKZhN2ccTMhitVYhdKaqTeHCiHl5sidHcOnJl9wQYLNvuCDRaM-Iv7qe7gP40i8OoI2OTs0EW8RZ_-croSgqkaueLAJRyNPcR76f5n_BsBFMDc</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1553090548</pqid></control><display><type>article</type><title>Epidermal growth factor receptor (EGFR) and prostaglandin-endoperoxide synthase 2 (PTGS2) are prognostic biomarkers for patients with resected colorectal cancer liver metastases</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><source>Nature Journals Online</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Goos, J A C M ; Hiemstra, A C ; Coupé, V M H ; Diosdado, B ; Kooijman, W ; Delis-Van Diemen, P M ; Karga, C ; Beliën, J A M ; Menke-van der Houven van Oordt, C W ; Geldof, A A ; Meijer, G A ; Hoekstra, O S ; Fijneman, R J A</creator><creatorcontrib>Goos, J A C M ; Hiemstra, A C ; Coupé, V M H ; Diosdado, B ; Kooijman, W ; Delis-Van Diemen, P M ; Karga, C ; Beliën, J A M ; Menke-van der Houven van Oordt, C W ; Geldof, A A ; Meijer, G A ; Hoekstra, O S ; Fijneman, R J A ; DeCoDe PET group ; the DeCoDe PET group</creatorcontrib><description>Background:
Resection of colorectal cancer liver metastasis (CRCLM) with curative intent has long-term benefit in ∼40% of cases. Prognostic biomarkers are needed to improve clinical management and reduce futile surgeries. Expression of epidermal growth factor receptor (EGFR) and prostaglandin-endoperoxide synthase 2 (PTGS2; also known as cyclooxygenase-2) has been associated with carcinogenesis and survival. We investigated the prognostic value of EGFR and PTGS2 expression in patients with resected CRCLM.
Methods:
Formalin-fixed paraffin-embedded CRCLM tissue and corresponding primary tumour specimens from a multi-institutional cohort of patients who underwent liver resection between 1990 and 2010 were incorporated into tissue microarrays (TMAs). TMAs were stained for EGFR and PTGS2 by immunohistochemistry. The hazard rate ratio (HRR) for the association between expression in CRCLM and overall survival was calculated using a 500-fold cross-validation procedure.
Results:
EGFR and PTGS2 expression could be evaluated in 323 and 351 patients, respectively. EGFR expression in CRCLM was associated with poor prognosis (HRR 1.54;
P
<0.01) with a cross-validated HRR of 1.47 (
P
=0.03). PTGS2 expression was also associated with poor prognosis (HRR 1.60;
P
<0.01) with a cross-validated HRR of 1.63 (
P
<0.01). Expression of EGFR and PTGS2 remained prognostic after multivariate analysis with standard clinicopathological variables (cross-validated HRR 1.51;
P
=0.02 and cross-validated HRR 1.59;
P
=0.01, respectively). Stratification for the commonly applied systemic therapy regimens demonstrated prognostic value for EGFR and PTGS2 only in the subgroup of patients who were not treated with systemic therapy (HRR 1.78;
P
<0.01 and HRR 1.64;
P
=0.04, respectively), with worst prognosis when both EGFR and PTGS2 were highly expressed (HRR 3.08;
P
<0.01). Expression of PTGS2 in CRCLM was correlated to expression in patient-matched primary tumours (
P
=0.02, 69.2% concordance).
Conclusions:
EGFR and PTGS2 expressions are prognostic molecular biomarkers with added value to standard clinicopathological variables for patients with resectable CRCLM.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/bjc.2014.354</identifier><identifier>PMID: 24983372</identifier><identifier>CODEN: BJCAAI</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>692/53/2422 ; 692/699/67/1504/1885 ; 692/699/67/322 ; Adult ; Aged ; Aged, 80 and over ; Biological and medical sciences ; Biomarkers ; Biomarkers, Tumor - metabolism ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Colorectal cancer ; Colorectal Neoplasms - metabolism ; Colorectal Neoplasms - mortality ; Colorectal Neoplasms - pathology ; Colorectal Neoplasms - surgery ; Cyclooxygenase 2 - metabolism ; Drug Resistance ; Epidemiology ; Epidermal growth factor ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; Humans ; Kaplan-Meier Estimate ; Liver ; Liver Neoplasms - metabolism ; Liver Neoplasms - mortality ; Liver Neoplasms - secondary ; Liver Neoplasms - surgery ; Male ; Medical prognosis ; Medical sciences ; Metastasis ; Middle Aged ; Molecular Diagnostics ; Molecular Medicine ; Multiple tumors. Solid tumors. Tumors in childhood (general aspects) ; Mutation ; Oncology ; Patients ; Receptor, Epidermal Growth Factor - metabolism ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Tumors ; Young Adult</subject><ispartof>British journal of cancer, 2014-08, Vol.111 (4), p.749-755</ispartof><rights>The Author(s) 2014</rights><rights>2015 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Aug 12, 2014</rights><rights>Copyright © 2014 Cancer Research UK 2014 Cancer Research UK</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c550t-47f057841bd1ac46a3a8f68006208e78447ffd24ec4013277a7986df80cab1b23</citedby><cites>FETCH-LOGICAL-c550t-47f057841bd1ac46a3a8f68006208e78447ffd24ec4013277a7986df80cab1b23</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/PMC4134500/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4134500/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41464,42533,51294,53766,53768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28722059$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24983372$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Goos, J A C M</creatorcontrib><creatorcontrib>Hiemstra, A C</creatorcontrib><creatorcontrib>Coupé, V M H</creatorcontrib><creatorcontrib>Diosdado, B</creatorcontrib><creatorcontrib>Kooijman, W</creatorcontrib><creatorcontrib>Delis-Van Diemen, P M</creatorcontrib><creatorcontrib>Karga, C</creatorcontrib><creatorcontrib>Beliën, J A M</creatorcontrib><creatorcontrib>Menke-van der Houven van Oordt, C W</creatorcontrib><creatorcontrib>Geldof, A A</creatorcontrib><creatorcontrib>Meijer, G A</creatorcontrib><creatorcontrib>Hoekstra, O S</creatorcontrib><creatorcontrib>Fijneman, R J A</creatorcontrib><creatorcontrib>DeCoDe PET group</creatorcontrib><creatorcontrib>the DeCoDe PET group</creatorcontrib><title>Epidermal growth factor receptor (EGFR) and prostaglandin-endoperoxide synthase 2 (PTGS2) are prognostic biomarkers for patients with resected colorectal cancer liver metastases</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Background:
Resection of colorectal cancer liver metastasis (CRCLM) with curative intent has long-term benefit in ∼40% of cases. Prognostic biomarkers are needed to improve clinical management and reduce futile surgeries. Expression of epidermal growth factor receptor (EGFR) and prostaglandin-endoperoxide synthase 2 (PTGS2; also known as cyclooxygenase-2) has been associated with carcinogenesis and survival. We investigated the prognostic value of EGFR and PTGS2 expression in patients with resected CRCLM.
Methods:
Formalin-fixed paraffin-embedded CRCLM tissue and corresponding primary tumour specimens from a multi-institutional cohort of patients who underwent liver resection between 1990 and 2010 were incorporated into tissue microarrays (TMAs). TMAs were stained for EGFR and PTGS2 by immunohistochemistry. The hazard rate ratio (HRR) for the association between expression in CRCLM and overall survival was calculated using a 500-fold cross-validation procedure.
Results:
EGFR and PTGS2 expression could be evaluated in 323 and 351 patients, respectively. EGFR expression in CRCLM was associated with poor prognosis (HRR 1.54;
P
<0.01) with a cross-validated HRR of 1.47 (
P
=0.03). PTGS2 expression was also associated with poor prognosis (HRR 1.60;
P
<0.01) with a cross-validated HRR of 1.63 (
P
<0.01). Expression of EGFR and PTGS2 remained prognostic after multivariate analysis with standard clinicopathological variables (cross-validated HRR 1.51;
P
=0.02 and cross-validated HRR 1.59;
P
=0.01, respectively). Stratification for the commonly applied systemic therapy regimens demonstrated prognostic value for EGFR and PTGS2 only in the subgroup of patients who were not treated with systemic therapy (HRR 1.78;
P
<0.01 and HRR 1.64;
P
=0.04, respectively), with worst prognosis when both EGFR and PTGS2 were highly expressed (HRR 3.08;
P
<0.01). Expression of PTGS2 in CRCLM was correlated to expression in patient-matched primary tumours (
P
=0.02, 69.2% concordance).
Conclusions:
EGFR and PTGS2 expressions are prognostic molecular biomarkers with added value to standard clinicopathological variables for patients with resectable CRCLM.</description><subject>692/53/2422</subject><subject>692/699/67/1504/1885</subject><subject>692/699/67/322</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biological and medical sciences</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Colorectal cancer</subject><subject>Colorectal Neoplasms - metabolism</subject><subject>Colorectal Neoplasms - mortality</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Colorectal Neoplasms - surgery</subject><subject>Cyclooxygenase 2 - metabolism</subject><subject>Drug Resistance</subject><subject>Epidemiology</subject><subject>Epidermal growth factor</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Humans</subject><subject>Kaplan-Meier Estimate</subject><subject>Liver</subject><subject>Liver Neoplasms - metabolism</subject><subject>Liver Neoplasms - mortality</subject><subject>Liver Neoplasms - secondary</subject><subject>Liver Neoplasms - surgery</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medical sciences</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Molecular Diagnostics</subject><subject>Molecular Medicine</subject><subject>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</subject><subject>Mutation</subject><subject>Oncology</subject><subject>Patients</subject><subject>Receptor, Epidermal Growth Factor - metabolism</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</subject><subject>Tumors</subject><subject>Young Adult</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptkVGL1DAUhYMo7rj65rMERFjBjkmaTNMXQZbZUVhQdH0OaXrbydhpapLZdX-W_9A7zLiu4Eubcr97zmkOIc85m3NW6rfNxs0F43JeKvmAzLgqRcG1qB6SGWOsKlgt2Al5ktIGP2umq8fkRMhal2UlZuTXcvItxK0daB_DTV7TzrocIo3gYNofzpariy-vqR1bOsWQsu0HPPuxgLENE8TwEwVouh3z2iaggp59vlp9FbgRYb_Rj7jkHW182Nr4HWKiHcpONnsYc6I3Hk0jJHAZWurCENA6Yx5nRweRDv4an1vIFr0TpKfkUWeHBM-O71Py7WJ5df6huPy0-nj-_rJwSrFcyKpjqtKSNy23Ti5saXW30IwtBNOAAwS6VkhwkvFSVJWtar1oO82cbXgjylPy7qA77ZottA7DRjuYKXr8jVsTrDf_Tka_Nn24NpKXUjGGAi-PAjH82EHKZhN2ccTMhitVYhdKaqTeHCiHl5sidHcOnJl9wQYLNvuCDRaM-Iv7qe7gP40i8OoI2OTs0EW8RZ_-croSgqkaueLAJRyNPcR76f5n_BsBFMDc</recordid><startdate>20140812</startdate><enddate>20140812</enddate><creator>Goos, J A C M</creator><creator>Hiemstra, A C</creator><creator>Coupé, V M H</creator><creator>Diosdado, B</creator><creator>Kooijman, W</creator><creator>Delis-Van Diemen, P M</creator><creator>Karga, C</creator><creator>Beliën, J A M</creator><creator>Menke-van der Houven van Oordt, C W</creator><creator>Geldof, A A</creator><creator>Meijer, G A</creator><creator>Hoekstra, O S</creator><creator>Fijneman, R J A</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>5PM</scope></search><sort><creationdate>20140812</creationdate><title>Epidermal growth factor receptor (EGFR) and prostaglandin-endoperoxide synthase 2 (PTGS2) are prognostic biomarkers for patients with resected colorectal cancer liver metastases</title><author>Goos, J A C M ; Hiemstra, A C ; Coupé, V M H ; Diosdado, B ; Kooijman, W ; Delis-Van Diemen, P M ; Karga, C ; Beliën, J A M ; Menke-van der Houven van Oordt, C W ; Geldof, A A ; Meijer, G A ; Hoekstra, O S ; Fijneman, R J A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c550t-47f057841bd1ac46a3a8f68006208e78447ffd24ec4013277a7986df80cab1b23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>692/53/2422</topic><topic>692/699/67/1504/1885</topic><topic>692/699/67/322</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biological and medical sciences</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Colorectal cancer</topic><topic>Colorectal Neoplasms - metabolism</topic><topic>Colorectal Neoplasms - mortality</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Colorectal Neoplasms - surgery</topic><topic>Cyclooxygenase 2 - metabolism</topic><topic>Drug Resistance</topic><topic>Epidemiology</topic><topic>Epidermal growth factor</topic><topic>Female</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Humans</topic><topic>Kaplan-Meier Estimate</topic><topic>Liver</topic><topic>Liver Neoplasms - metabolism</topic><topic>Liver Neoplasms - mortality</topic><topic>Liver Neoplasms - secondary</topic><topic>Liver Neoplasms - surgery</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medical sciences</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Molecular Diagnostics</topic><topic>Molecular Medicine</topic><topic>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</topic><topic>Mutation</topic><topic>Oncology</topic><topic>Patients</topic><topic>Receptor, Epidermal Growth Factor - metabolism</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</topic><topic>Tumors</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Goos, J A C M</creatorcontrib><creatorcontrib>Hiemstra, A C</creatorcontrib><creatorcontrib>Coupé, V M H</creatorcontrib><creatorcontrib>Diosdado, B</creatorcontrib><creatorcontrib>Kooijman, W</creatorcontrib><creatorcontrib>Delis-Van Diemen, P M</creatorcontrib><creatorcontrib>Karga, C</creatorcontrib><creatorcontrib>Beliën, J A M</creatorcontrib><creatorcontrib>Menke-van der Houven van Oordt, C W</creatorcontrib><creatorcontrib>Geldof, A A</creatorcontrib><creatorcontrib>Meijer, G A</creatorcontrib><creatorcontrib>Hoekstra, O S</creatorcontrib><creatorcontrib>Fijneman, R J A</creatorcontrib><creatorcontrib>DeCoDe PET group</creatorcontrib><creatorcontrib>the DeCoDe PET group</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>PubMed Central (Full Participant titles)</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Goos, J A C M</au><au>Hiemstra, A C</au><au>Coupé, V M H</au><au>Diosdado, B</au><au>Kooijman, W</au><au>Delis-Van Diemen, P M</au><au>Karga, C</au><au>Beliën, J A M</au><au>Menke-van der Houven van Oordt, C W</au><au>Geldof, A A</au><au>Meijer, G A</au><au>Hoekstra, O S</au><au>Fijneman, R J A</au><aucorp>DeCoDe PET group</aucorp><aucorp>the DeCoDe PET group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Epidermal growth factor receptor (EGFR) and prostaglandin-endoperoxide synthase 2 (PTGS2) are prognostic biomarkers for patients with resected colorectal cancer liver metastases</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2014-08-12</date><risdate>2014</risdate><volume>111</volume><issue>4</issue><spage>749</spage><epage>755</epage><pages>749-755</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><coden>BJCAAI</coden><abstract>Background:
Resection of colorectal cancer liver metastasis (CRCLM) with curative intent has long-term benefit in ∼40% of cases. Prognostic biomarkers are needed to improve clinical management and reduce futile surgeries. Expression of epidermal growth factor receptor (EGFR) and prostaglandin-endoperoxide synthase 2 (PTGS2; also known as cyclooxygenase-2) has been associated with carcinogenesis and survival. We investigated the prognostic value of EGFR and PTGS2 expression in patients with resected CRCLM.
Methods:
Formalin-fixed paraffin-embedded CRCLM tissue and corresponding primary tumour specimens from a multi-institutional cohort of patients who underwent liver resection between 1990 and 2010 were incorporated into tissue microarrays (TMAs). TMAs were stained for EGFR and PTGS2 by immunohistochemistry. The hazard rate ratio (HRR) for the association between expression in CRCLM and overall survival was calculated using a 500-fold cross-validation procedure.
Results:
EGFR and PTGS2 expression could be evaluated in 323 and 351 patients, respectively. EGFR expression in CRCLM was associated with poor prognosis (HRR 1.54;
P
<0.01) with a cross-validated HRR of 1.47 (
P
=0.03). PTGS2 expression was also associated with poor prognosis (HRR 1.60;
P
<0.01) with a cross-validated HRR of 1.63 (
P
<0.01). Expression of EGFR and PTGS2 remained prognostic after multivariate analysis with standard clinicopathological variables (cross-validated HRR 1.51;
P
=0.02 and cross-validated HRR 1.59;
P
=0.01, respectively). Stratification for the commonly applied systemic therapy regimens demonstrated prognostic value for EGFR and PTGS2 only in the subgroup of patients who were not treated with systemic therapy (HRR 1.78;
P
<0.01 and HRR 1.64;
P
=0.04, respectively), with worst prognosis when both EGFR and PTGS2 were highly expressed (HRR 3.08;
P
<0.01). Expression of PTGS2 in CRCLM was correlated to expression in patient-matched primary tumours (
P
=0.02, 69.2% concordance).
Conclusions:
EGFR and PTGS2 expressions are prognostic molecular biomarkers with added value to standard clinicopathological variables for patients with resectable CRCLM.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>24983372</pmid><doi>10.1038/bjc.2014.354</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0007-0920 |
| ispartof | British journal of cancer, 2014-08, Vol.111 (4), p.749-755 |
| issn | 0007-0920 1532-1827 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4134500 |
| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature Journals Online; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | 692/53/2422 692/699/67/1504/1885 692/699/67/322 Adult Aged Aged, 80 and over Biological and medical sciences Biomarkers Biomarkers, Tumor - metabolism Biomedical and Life Sciences Biomedicine Cancer Research Colorectal cancer Colorectal Neoplasms - metabolism Colorectal Neoplasms - mortality Colorectal Neoplasms - pathology Colorectal Neoplasms - surgery Cyclooxygenase 2 - metabolism Drug Resistance Epidemiology Epidermal growth factor Female Gastroenterology. Liver. Pancreas. Abdomen Humans Kaplan-Meier Estimate Liver Liver Neoplasms - metabolism Liver Neoplasms - mortality Liver Neoplasms - secondary Liver Neoplasms - surgery Male Medical prognosis Medical sciences Metastasis Middle Aged Molecular Diagnostics Molecular Medicine Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Mutation Oncology Patients Receptor, Epidermal Growth Factor - metabolism Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Tumors Young Adult |
| title | Epidermal growth factor receptor (EGFR) and prostaglandin-endoperoxide synthase 2 (PTGS2) are prognostic biomarkers for patients with resected colorectal cancer liver metastases |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T23%3A30%3A38IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Epidermal%20growth%20factor%20receptor%20(EGFR)%20and%20prostaglandin-endoperoxide%20synthase%202%20(PTGS2)%20are%20prognostic%20biomarkers%20for%20patients%20with%20resected%20colorectal%20cancer%20liver%20metastases&rft.jtitle=British%20journal%20of%20cancer&rft.au=Goos,%20J%20A%20C%20M&rft.aucorp=DeCoDe%20PET%20group&rft.date=2014-08-12&rft.volume=111&rft.issue=4&rft.spage=749&rft.epage=755&rft.pages=749-755&rft.issn=0007-0920&rft.eissn=1532-1827&rft.coden=BJCAAI&rft_id=info:doi/10.1038/bjc.2014.354&rft_dat=%3Cproquest_pubme%3E3402049801%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1553090548&rft_id=info:pmid/24983372&rfr_iscdi=true |