The relationship between the Glasgow Microenvironment Score and Markers of Epithelial-to-Mesenchymal Transition in TNM II-III Colorectal Cancer

Recently published work on the Glasgow Microenvironment Score (GMS) demonstrated its relevance as a biomarker in TNM II-III colorectal cancer (CRC). Epithelial-to-Mesenchymal Transition (EMT) markers in colorectal cancer have also shown promise as prognostic biomarkers. This study aimed to assess th...

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Veröffentlicht in:Human pathology 2022-09, Vol.127, p.1-11
Hauptverfasser: Alexander, Peter G., Matly, Amna A.M., Jirapongwattana, Niphat, Pennel, Kathryn A.F., van Wyk, Hester C., McMillan, Donald C., Horgan, Paul G., Roxburgh, Campbell S.D., Thuwajit, Chanitra, Roseweir, Antonia K., Quinn, Jean, Park, James H., Edwards, Joanne
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container_title Human pathology
container_volume 127
creator Alexander, Peter G.
Matly, Amna A.M.
Jirapongwattana, Niphat
Pennel, Kathryn A.F.
van Wyk, Hester C.
McMillan, Donald C.
Horgan, Paul G.
Roxburgh, Campbell S.D.
Thuwajit, Chanitra
Roseweir, Antonia K.
Quinn, Jean
Park, James H.
Edwards, Joanne
description Recently published work on the Glasgow Microenvironment Score (GMS) demonstrated its relevance as a biomarker in TNM II-III colorectal cancer (CRC). Epithelial-to-Mesenchymal Transition (EMT) markers in colorectal cancer have also shown promise as prognostic biomarkers. This study aimed to assess the relationship between GMS and markers of EMT in stage II-III CRC. A previously constructed tissue microarray of CRC tumours resected between 2000 and 2007 from the Western Infirmary, Stobhill and Gartnavel General hospitals in Glasgow was used. Immunohistochemistry was performed for five markers of EMT: E-cadherin, B-catenin, Fascin, Snail and Zeb1. Two-hundred and thirty-eight TNM II-III CRC with valid scores for all EMT markers and GMS were assessed. The prognostic significance of markers of EMT in this cohort and relationships between GMS and markers of EMT were determined. High cytoplasmic and nuclear B-catenin and membrane Zeb-1 were significant for worse CSS (HR 1.67, 95% CI 1.01-2.76, p
doi_str_mv 10.1016/j.humpath.2022.05.012
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Epithelial-to-Mesenchymal Transition (EMT) markers in colorectal cancer have also shown promise as prognostic biomarkers. This study aimed to assess the relationship between GMS and markers of EMT in stage II-III CRC. A previously constructed tissue microarray of CRC tumours resected between 2000 and 2007 from the Western Infirmary, Stobhill and Gartnavel General hospitals in Glasgow was used. Immunohistochemistry was performed for five markers of EMT: E-cadherin, B-catenin, Fascin, Snail and Zeb1. Two-hundred and thirty-eight TNM II-III CRC with valid scores for all EMT markers and GMS were assessed. The prognostic significance of markers of EMT in this cohort and relationships between GMS and markers of EMT were determined. High cytoplasmic and nuclear B-catenin and membrane Zeb-1 were significant for worse CSS (HR 1.67, 95% CI 1.01-2.76, p&lt;0.05; HR 2.22, 95% CI 1.24-3.97, p&lt;0.01; and HR 2.00, 95% CI 1.07-3.77, p=0.03, respectively). GMS 0 associated with low membrane Fascin (p=0.03), whereas membrane and cytoplasmic Fascin were observed to be highest in GMS 1, but lower in GMS 2. Nuclear B-catenin was lowest in GMS 0, but highest in GMS 2 (p=0.03), in keeping with its role in facilitating EMT. Novel associations were demonstrated between GMS categories and markers of EMT, particularly B-catenin and Fascin, which require further investigation in independent cohorts. •Novel associations are demonstrated between the GMS and markers of EMT in CRC.•EMT markers B-catenin and Zeb-1 demonstrated to associate with survival.•Nuclear B-catenin is demonstrated to associate with GMS as a whole.•Membrane Fascin was significantly lower in GMS 0.•These novel associations provide recommendations for future research.</description><identifier>ISSN: 0046-8177</identifier><identifier>EISSN: 1532-8392</identifier><identifier>DOI: 10.1016/j.humpath.2022.05.012</identifier><identifier>PMID: 35623467</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Antibodies ; Cell adhesion &amp; migration ; Chemotherapy ; Colorectal cancer ; Cytoskeleton ; Epithelial-to-Mesenchymal Transition (EMT) ; Genotype &amp; phenotype ; Laboratories ; Medical prognosis ; Metastasis ; Pathology ; Proteins ; Surgery ; survival ; Tumors ; Tumour Microenvironment</subject><ispartof>Human pathology, 2022-09, Vol.127, p.1-11</ispartof><rights>2022</rights><rights>Copyright © 2022. Published by Elsevier Inc.</rights><rights>2022. The Authors</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c370t-5ba9488724dad4ffe111d5d0645bb1abbc210554d26dc4fefed84a37303d73a53</citedby><cites>FETCH-LOGICAL-c370t-5ba9488724dad4ffe111d5d0645bb1abbc210554d26dc4fefed84a37303d73a53</cites><orcidid>0000-0002-6123-4922</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S004681772200140X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35623467$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Alexander, Peter G.</creatorcontrib><creatorcontrib>Matly, Amna A.M.</creatorcontrib><creatorcontrib>Jirapongwattana, Niphat</creatorcontrib><creatorcontrib>Pennel, Kathryn A.F.</creatorcontrib><creatorcontrib>van Wyk, Hester C.</creatorcontrib><creatorcontrib>McMillan, Donald C.</creatorcontrib><creatorcontrib>Horgan, Paul G.</creatorcontrib><creatorcontrib>Roxburgh, Campbell S.D.</creatorcontrib><creatorcontrib>Thuwajit, Chanitra</creatorcontrib><creatorcontrib>Roseweir, Antonia K.</creatorcontrib><creatorcontrib>Quinn, Jean</creatorcontrib><creatorcontrib>Park, James H.</creatorcontrib><creatorcontrib>Edwards, Joanne</creatorcontrib><title>The relationship between the Glasgow Microenvironment Score and Markers of Epithelial-to-Mesenchymal Transition in TNM II-III Colorectal Cancer</title><title>Human pathology</title><addtitle>Hum Pathol</addtitle><description>Recently published work on the Glasgow Microenvironment Score (GMS) demonstrated its relevance as a biomarker in TNM II-III colorectal cancer (CRC). Epithelial-to-Mesenchymal Transition (EMT) markers in colorectal cancer have also shown promise as prognostic biomarkers. This study aimed to assess the relationship between GMS and markers of EMT in stage II-III CRC. A previously constructed tissue microarray of CRC tumours resected between 2000 and 2007 from the Western Infirmary, Stobhill and Gartnavel General hospitals in Glasgow was used. Immunohistochemistry was performed for five markers of EMT: E-cadherin, B-catenin, Fascin, Snail and Zeb1. Two-hundred and thirty-eight TNM II-III CRC with valid scores for all EMT markers and GMS were assessed. The prognostic significance of markers of EMT in this cohort and relationships between GMS and markers of EMT were determined. High cytoplasmic and nuclear B-catenin and membrane Zeb-1 were significant for worse CSS (HR 1.67, 95% CI 1.01-2.76, p&lt;0.05; HR 2.22, 95% CI 1.24-3.97, p&lt;0.01; and HR 2.00, 95% CI 1.07-3.77, p=0.03, respectively). GMS 0 associated with low membrane Fascin (p=0.03), whereas membrane and cytoplasmic Fascin were observed to be highest in GMS 1, but lower in GMS 2. Nuclear B-catenin was lowest in GMS 0, but highest in GMS 2 (p=0.03), in keeping with its role in facilitating EMT. Novel associations were demonstrated between GMS categories and markers of EMT, particularly B-catenin and Fascin, which require further investigation in independent cohorts. •Novel associations are demonstrated between the GMS and markers of EMT in CRC.•EMT markers B-catenin and Zeb-1 demonstrated to associate with survival.•Nuclear B-catenin is demonstrated to associate with GMS as a whole.•Membrane Fascin was significantly lower in GMS 0.•These novel associations provide recommendations for future research.</description><subject>Antibodies</subject><subject>Cell adhesion &amp; migration</subject><subject>Chemotherapy</subject><subject>Colorectal cancer</subject><subject>Cytoskeleton</subject><subject>Epithelial-to-Mesenchymal Transition (EMT)</subject><subject>Genotype &amp; phenotype</subject><subject>Laboratories</subject><subject>Medical prognosis</subject><subject>Metastasis</subject><subject>Pathology</subject><subject>Proteins</subject><subject>Surgery</subject><subject>survival</subject><subject>Tumors</subject><subject>Tumour Microenvironment</subject><issn>0046-8177</issn><issn>1532-8392</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNqFkc1u1DAUhS0EokPhEUCW2HST4N84XSE0KiVSBxYMa8uJb4iHxA520qpPwSvj0Qws2LC6i_udc6_OQeg1JSUltHp3KId1ms0ylIwwVhJZEsqeoA2VnBU1v2ZP0YYQURU1VeoCvUjpQAilUsjn6ILLinFRqQ36tR8ARxjN4oJPg5txC8sDgMdLXtyOJn0PD3jnuhjA37sY_AR-wV-7EAEbb_HOxB8QEw49vpldFo3OjMUSih0k8N3wOJkR76PxyR1PYOfx_vMON03RNA3ehjEbdUtmtsZ3EF-iZ70ZE7w6z0v07ePNfvupuPty22w_3BUdV2QpZGuuRV0rJqyxou-BUmqlJZWQbUtN23aMEimFZZXtRA892FoYrjjhVnEj-SW6OvnOMfxcIS16cqmDcTQewpo0qxRlqqJcZPTtP-ghrNHn7zRTVCguJSGZkicqJ5VShF7P0U0mPmpK9LExfdDnxvSxMU2kzo1l3Zuz-9pOYP-q_lSUgfcnAHIc9w6iTp3LyYJ1x-S0De4_J34D8IirQQ</recordid><startdate>20220901</startdate><enddate>20220901</enddate><creator>Alexander, Peter G.</creator><creator>Matly, Amna A.M.</creator><creator>Jirapongwattana, Niphat</creator><creator>Pennel, Kathryn A.F.</creator><creator>van Wyk, Hester C.</creator><creator>McMillan, Donald C.</creator><creator>Horgan, Paul G.</creator><creator>Roxburgh, Campbell S.D.</creator><creator>Thuwajit, Chanitra</creator><creator>Roseweir, Antonia K.</creator><creator>Quinn, Jean</creator><creator>Park, James H.</creator><creator>Edwards, Joanne</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-6123-4922</orcidid></search><sort><creationdate>20220901</creationdate><title>The relationship between the Glasgow Microenvironment Score and Markers of Epithelial-to-Mesenchymal Transition in TNM II-III Colorectal Cancer</title><author>Alexander, Peter G. ; Matly, Amna A.M. ; Jirapongwattana, Niphat ; Pennel, Kathryn A.F. ; van Wyk, Hester C. ; McMillan, Donald C. ; Horgan, Paul G. ; Roxburgh, Campbell S.D. ; Thuwajit, Chanitra ; Roseweir, Antonia K. ; Quinn, Jean ; Park, James H. ; Edwards, Joanne</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c370t-5ba9488724dad4ffe111d5d0645bb1abbc210554d26dc4fefed84a37303d73a53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Antibodies</topic><topic>Cell adhesion &amp; migration</topic><topic>Chemotherapy</topic><topic>Colorectal cancer</topic><topic>Cytoskeleton</topic><topic>Epithelial-to-Mesenchymal Transition (EMT)</topic><topic>Genotype &amp; phenotype</topic><topic>Laboratories</topic><topic>Medical prognosis</topic><topic>Metastasis</topic><topic>Pathology</topic><topic>Proteins</topic><topic>Surgery</topic><topic>survival</topic><topic>Tumors</topic><topic>Tumour Microenvironment</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Alexander, Peter G.</creatorcontrib><creatorcontrib>Matly, Amna A.M.</creatorcontrib><creatorcontrib>Jirapongwattana, Niphat</creatorcontrib><creatorcontrib>Pennel, Kathryn A.F.</creatorcontrib><creatorcontrib>van Wyk, Hester C.</creatorcontrib><creatorcontrib>McMillan, Donald C.</creatorcontrib><creatorcontrib>Horgan, Paul G.</creatorcontrib><creatorcontrib>Roxburgh, Campbell S.D.</creatorcontrib><creatorcontrib>Thuwajit, Chanitra</creatorcontrib><creatorcontrib>Roseweir, Antonia K.</creatorcontrib><creatorcontrib>Quinn, Jean</creatorcontrib><creatorcontrib>Park, James H.</creatorcontrib><creatorcontrib>Edwards, Joanne</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Human pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Alexander, Peter G.</au><au>Matly, Amna A.M.</au><au>Jirapongwattana, Niphat</au><au>Pennel, Kathryn A.F.</au><au>van Wyk, Hester C.</au><au>McMillan, Donald C.</au><au>Horgan, Paul G.</au><au>Roxburgh, Campbell S.D.</au><au>Thuwajit, Chanitra</au><au>Roseweir, Antonia K.</au><au>Quinn, Jean</au><au>Park, James H.</au><au>Edwards, Joanne</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The relationship between the Glasgow Microenvironment Score and Markers of Epithelial-to-Mesenchymal Transition in TNM II-III Colorectal Cancer</atitle><jtitle>Human pathology</jtitle><addtitle>Hum Pathol</addtitle><date>2022-09-01</date><risdate>2022</risdate><volume>127</volume><spage>1</spage><epage>11</epage><pages>1-11</pages><issn>0046-8177</issn><eissn>1532-8392</eissn><abstract>Recently published work on the Glasgow Microenvironment Score (GMS) demonstrated its relevance as a biomarker in TNM II-III colorectal cancer (CRC). Epithelial-to-Mesenchymal Transition (EMT) markers in colorectal cancer have also shown promise as prognostic biomarkers. This study aimed to assess the relationship between GMS and markers of EMT in stage II-III CRC. A previously constructed tissue microarray of CRC tumours resected between 2000 and 2007 from the Western Infirmary, Stobhill and Gartnavel General hospitals in Glasgow was used. Immunohistochemistry was performed for five markers of EMT: E-cadherin, B-catenin, Fascin, Snail and Zeb1. Two-hundred and thirty-eight TNM II-III CRC with valid scores for all EMT markers and GMS were assessed. The prognostic significance of markers of EMT in this cohort and relationships between GMS and markers of EMT were determined. High cytoplasmic and nuclear B-catenin and membrane Zeb-1 were significant for worse CSS (HR 1.67, 95% CI 1.01-2.76, p&lt;0.05; HR 2.22, 95% CI 1.24-3.97, p&lt;0.01; and HR 2.00, 95% CI 1.07-3.77, p=0.03, respectively). GMS 0 associated with low membrane Fascin (p=0.03), whereas membrane and cytoplasmic Fascin were observed to be highest in GMS 1, but lower in GMS 2. Nuclear B-catenin was lowest in GMS 0, but highest in GMS 2 (p=0.03), in keeping with its role in facilitating EMT. Novel associations were demonstrated between GMS categories and markers of EMT, particularly B-catenin and Fascin, which require further investigation in independent cohorts. •Novel associations are demonstrated between the GMS and markers of EMT in CRC.•EMT markers B-catenin and Zeb-1 demonstrated to associate with survival.•Nuclear B-catenin is demonstrated to associate with GMS as a whole.•Membrane Fascin was significantly lower in GMS 0.•These novel associations provide recommendations for future research.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>35623467</pmid><doi>10.1016/j.humpath.2022.05.012</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-6123-4922</orcidid><oa>free_for_read</oa></addata></record>
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subjects Antibodies
Cell adhesion & migration
Chemotherapy
Colorectal cancer
Cytoskeleton
Epithelial-to-Mesenchymal Transition (EMT)
Genotype & phenotype
Laboratories
Medical prognosis
Metastasis
Pathology
Proteins
Surgery
survival
Tumors
Tumour Microenvironment
title The relationship between the Glasgow Microenvironment Score and Markers of Epithelial-to-Mesenchymal Transition in TNM II-III Colorectal Cancer
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