Tumour budding/T cell infiltrates in colorectal cancer: proposal of a novel combined score
Aims The tumour–node–metastasis classification system is used for prognostication purposes and to guide patient management. However, in colorectal cancer (CRC), additional markers are needed to stratify prognostic subgroups. Two promising markers have emerged from large bodies of research: tumour bu...
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| Veröffentlicht in: | Histopathology 2020-03, Vol.76 (4), p.572-580 |
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| container_title | Histopathology |
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| creator | Dawson, Heather Christe, Lucine Eichmann, Micha Reinhard, Stefan Zlobec, Inti Blank, Annika Lugli, Alessandro |
| description | Aims
The tumour–node–metastasis classification system is used for prognostication purposes and to guide patient management. However, in colorectal cancer (CRC), additional markers are needed to stratify prognostic subgroups. Two promising markers have emerged from large bodies of research: tumour budding and T cell host response (CD3, CD8 and CD45RO infiltrates). However, attempts to combine these two parameters have been sparse. The aim of this study was to perform an assessment of potential protagonists that could be used in a combined score (budding/T cell score, BTS).
Methods and results
This descriptive, retrospective study was performed on a multipunch tissue microarray containing material from 345 patients with stages I–IV CRC. Areas from tumour centre, front and microenvironment were stained for pancytokeratin/CD3, pancytokeratin/CD8 and pancytokeratin/CD45RO. Tumour buds were scored manually and T cell infiltrates digitally using open‐source software. Tumour buds, T cell counts and combined BTS were associated with clinicopathological features and overall survival (OS). A higher combined BTS score (buds/CD8, tumour centre) performed better than budding or CD8/CD3 alone in predicting nodal metastases (P |
| doi_str_mv | 10.1111/his.14006 |
| format | Article |
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The tumour–node–metastasis classification system is used for prognostication purposes and to guide patient management. However, in colorectal cancer (CRC), additional markers are needed to stratify prognostic subgroups. Two promising markers have emerged from large bodies of research: tumour budding and T cell host response (CD3, CD8 and CD45RO infiltrates). However, attempts to combine these two parameters have been sparse. The aim of this study was to perform an assessment of potential protagonists that could be used in a combined score (budding/T cell score, BTS).
Methods and results
This descriptive, retrospective study was performed on a multipunch tissue microarray containing material from 345 patients with stages I–IV CRC. Areas from tumour centre, front and microenvironment were stained for pancytokeratin/CD3, pancytokeratin/CD8 and pancytokeratin/CD45RO. Tumour buds were scored manually and T cell infiltrates digitally using open‐source software. Tumour buds, T cell counts and combined BTS were associated with clinicopathological features and overall survival (OS). A higher combined BTS score (buds/CD8, tumour centre) performed better than budding or CD8/CD3 alone in predicting nodal metastases (P < 0.0001, OR = 1.466, 95% CI = 1.115–1.928). Only higher BTS (buds/CD3) were significantly associated with poorer OS on multivariate analysis (P = 0.012, hazard ratio = 1.218, 95% confidence interval = 1.044–1.419).
Conclusions
Although CD8+/CD3+ T cells are predictive of tumour biology in CRC, we found a combined BTS to be stronger in predicting survival and certain features with high clinical relevance, such as nodal metastases, in comparison to budding or T cells alone. Further studies combining T cell infiltrates and tumour budding are necessary to optimise risk assessment of CRC.</description><identifier>ISSN: 0309-0167</identifier><identifier>EISSN: 1365-2559</identifier><identifier>DOI: 10.1111/his.14006</identifier><identifier>PMID: 31560788</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>CD3 antigen ; CD8 antigen ; Colorectal cancer ; Colorectal carcinoma ; host response ; Immunoscore ; Lymphocytes ; Lymphocytes T ; Metastases ; Metastasis ; Multivariate analysis ; Risk assessment ; Tumors ; tumour budding</subject><ispartof>Histopathology, 2020-03, Vol.76 (4), p.572-580</ispartof><rights>2019 John Wiley & Sons Ltd</rights><rights>2019 John Wiley & Sons Ltd.</rights><rights>Copyright © 2020 John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3886-cedb2f8c158f87e8bb8771d2897b64bc7ea2e988cd2095f1ebcf8b26e2ec7afc3</citedby><cites>FETCH-LOGICAL-c3886-cedb2f8c158f87e8bb8771d2897b64bc7ea2e988cd2095f1ebcf8b26e2ec7afc3</cites><orcidid>0000-0001-6283-659X ; 0000-0001-7527-336X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fhis.14006$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fhis.14006$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31560788$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dawson, Heather</creatorcontrib><creatorcontrib>Christe, Lucine</creatorcontrib><creatorcontrib>Eichmann, Micha</creatorcontrib><creatorcontrib>Reinhard, Stefan</creatorcontrib><creatorcontrib>Zlobec, Inti</creatorcontrib><creatorcontrib>Blank, Annika</creatorcontrib><creatorcontrib>Lugli, Alessandro</creatorcontrib><title>Tumour budding/T cell infiltrates in colorectal cancer: proposal of a novel combined score</title><title>Histopathology</title><addtitle>Histopathology</addtitle><description>Aims
The tumour–node–metastasis classification system is used for prognostication purposes and to guide patient management. However, in colorectal cancer (CRC), additional markers are needed to stratify prognostic subgroups. Two promising markers have emerged from large bodies of research: tumour budding and T cell host response (CD3, CD8 and CD45RO infiltrates). However, attempts to combine these two parameters have been sparse. The aim of this study was to perform an assessment of potential protagonists that could be used in a combined score (budding/T cell score, BTS).
Methods and results
This descriptive, retrospective study was performed on a multipunch tissue microarray containing material from 345 patients with stages I–IV CRC. Areas from tumour centre, front and microenvironment were stained for pancytokeratin/CD3, pancytokeratin/CD8 and pancytokeratin/CD45RO. Tumour buds were scored manually and T cell infiltrates digitally using open‐source software. Tumour buds, T cell counts and combined BTS were associated with clinicopathological features and overall survival (OS). A higher combined BTS score (buds/CD8, tumour centre) performed better than budding or CD8/CD3 alone in predicting nodal metastases (P < 0.0001, OR = 1.466, 95% CI = 1.115–1.928). Only higher BTS (buds/CD3) were significantly associated with poorer OS on multivariate analysis (P = 0.012, hazard ratio = 1.218, 95% confidence interval = 1.044–1.419).
Conclusions
Although CD8+/CD3+ T cells are predictive of tumour biology in CRC, we found a combined BTS to be stronger in predicting survival and certain features with high clinical relevance, such as nodal metastases, in comparison to budding or T cells alone. Further studies combining T cell infiltrates and tumour budding are necessary to optimise risk assessment of CRC.</description><subject>CD3 antigen</subject><subject>CD8 antigen</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>host response</subject><subject>Immunoscore</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Multivariate analysis</subject><subject>Risk assessment</subject><subject>Tumors</subject><subject>tumour budding</subject><issn>0309-0167</issn><issn>1365-2559</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp1kE1LAzEQhoMotn4c_AMS8KKHtUm2m2S9SfGjUPBgvXgJSXaiW3Y3Nekq_fdGWz0IzmWGmYeXd16ETii5pKlGr3W8pGNC-A4a0pwXGSuKchcNSU7KjFAuBuggxgUhVOSM7aNBTgtOhJRD9DzvW98HbPqqqruX0RxbaBpcd65uVkGvIKYZW9_4AHalG2x1ZyFc4WXwSx_TwjusceffId18a-oOKhxtwo_QntNNhONtP0RPtzfzyX02e7ibTq5nmc2l5JmFyjAnLS2kkwKkMVIIWjFZCsPHxgrQDEopbcVIWTgKxjppGAcGVmhn80N0vtFNlt56iCvV1vHrC92B76NirCxpXoxFmdCzP-giPd8ld4rlfCw5F0Qk6mJD2eBjDODUMtStDmtFifoKXKXA1XfgiT3dKvamheqX_Ek4AaMN8FE3sP5fSd1PHzeSn-1Lip8</recordid><startdate>202003</startdate><enddate>202003</enddate><creator>Dawson, Heather</creator><creator>Christe, Lucine</creator><creator>Eichmann, Micha</creator><creator>Reinhard, Stefan</creator><creator>Zlobec, Inti</creator><creator>Blank, Annika</creator><creator>Lugli, Alessandro</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-6283-659X</orcidid><orcidid>https://orcid.org/0000-0001-7527-336X</orcidid></search><sort><creationdate>202003</creationdate><title>Tumour budding/T cell infiltrates in colorectal cancer: proposal of a novel combined score</title><author>Dawson, Heather ; Christe, Lucine ; Eichmann, Micha ; Reinhard, Stefan ; Zlobec, Inti ; Blank, Annika ; Lugli, Alessandro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3886-cedb2f8c158f87e8bb8771d2897b64bc7ea2e988cd2095f1ebcf8b26e2ec7afc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>CD3 antigen</topic><topic>CD8 antigen</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>host response</topic><topic>Immunoscore</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Multivariate analysis</topic><topic>Risk assessment</topic><topic>Tumors</topic><topic>tumour budding</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dawson, Heather</creatorcontrib><creatorcontrib>Christe, Lucine</creatorcontrib><creatorcontrib>Eichmann, Micha</creatorcontrib><creatorcontrib>Reinhard, Stefan</creatorcontrib><creatorcontrib>Zlobec, Inti</creatorcontrib><creatorcontrib>Blank, Annika</creatorcontrib><creatorcontrib>Lugli, Alessandro</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Histopathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dawson, Heather</au><au>Christe, Lucine</au><au>Eichmann, Micha</au><au>Reinhard, Stefan</au><au>Zlobec, Inti</au><au>Blank, Annika</au><au>Lugli, Alessandro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tumour budding/T cell infiltrates in colorectal cancer: proposal of a novel combined score</atitle><jtitle>Histopathology</jtitle><addtitle>Histopathology</addtitle><date>2020-03</date><risdate>2020</risdate><volume>76</volume><issue>4</issue><spage>572</spage><epage>580</epage><pages>572-580</pages><issn>0309-0167</issn><eissn>1365-2559</eissn><abstract>Aims
The tumour–node–metastasis classification system is used for prognostication purposes and to guide patient management. However, in colorectal cancer (CRC), additional markers are needed to stratify prognostic subgroups. Two promising markers have emerged from large bodies of research: tumour budding and T cell host response (CD3, CD8 and CD45RO infiltrates). However, attempts to combine these two parameters have been sparse. The aim of this study was to perform an assessment of potential protagonists that could be used in a combined score (budding/T cell score, BTS).
Methods and results
This descriptive, retrospective study was performed on a multipunch tissue microarray containing material from 345 patients with stages I–IV CRC. Areas from tumour centre, front and microenvironment were stained for pancytokeratin/CD3, pancytokeratin/CD8 and pancytokeratin/CD45RO. Tumour buds were scored manually and T cell infiltrates digitally using open‐source software. Tumour buds, T cell counts and combined BTS were associated with clinicopathological features and overall survival (OS). A higher combined BTS score (buds/CD8, tumour centre) performed better than budding or CD8/CD3 alone in predicting nodal metastases (P < 0.0001, OR = 1.466, 95% CI = 1.115–1.928). Only higher BTS (buds/CD3) were significantly associated with poorer OS on multivariate analysis (P = 0.012, hazard ratio = 1.218, 95% confidence interval = 1.044–1.419).
Conclusions
Although CD8+/CD3+ T cells are predictive of tumour biology in CRC, we found a combined BTS to be stronger in predicting survival and certain features with high clinical relevance, such as nodal metastases, in comparison to budding or T cells alone. Further studies combining T cell infiltrates and tumour budding are necessary to optimise risk assessment of CRC.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>31560788</pmid><doi>10.1111/his.14006</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-6283-659X</orcidid><orcidid>https://orcid.org/0000-0001-7527-336X</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Wiley Online Library Journals Frontfile Complete |
| subjects | CD3 antigen CD8 antigen Colorectal cancer Colorectal carcinoma host response Immunoscore Lymphocytes Lymphocytes T Metastases Metastasis Multivariate analysis Risk assessment Tumors tumour budding |
| title | Tumour budding/T cell infiltrates in colorectal cancer: proposal of a novel combined score |
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