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The distribution of intratumoral macrophages correlates with molecular phenotypes and impacts prognosis in colorectal carcinoma
Aims The role of tumour‐associated macrophages (TAMs) in colorectal cancer (CRC) remains elusive. In this study, we aimed to examine the correlation between TAMs, clinicopathological features, tumour‐infiltrating lymphocytes (TILs) and prognosis in CRC by the use of image analysis. Methods and resul...
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| Published in: | Histopathology 2018-10, Vol.73 (4), p.663-671 |
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| container_issue | 4 |
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| container_title | Histopathology |
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| creator | Kim, Younghoon Wen, Xianyu Bae, Jeong M Kim, Jung H Cho, Nam‐Yun Kang, Gyeong H |
| description | Aims
The role of tumour‐associated macrophages (TAMs) in colorectal cancer (CRC) remains elusive. In this study, we aimed to examine the correlation between TAMs, clinicopathological features, tumour‐infiltrating lymphocytes (TILs) and prognosis in CRC by the use of image analysis.
Methods and results
Immunohistochemical staining for CD68 and CD163 was performed as pan‐macrophage and M2‐macrophage markers, respectively. Each marker was analysed separately for intra‐epithelial and stromal area densities. All four macrophage densities showed a significant correlation with one another (P = 0.001). Intra‐epithelial CD68+ macrophage densities showed a correlation with pTNM stage (P = 0.008), microsatellite instability (MSI) (P |
| doi_str_mv | 10.1111/his.13674 |
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| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2056389164</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2056389164</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3534-ffdc6b6d6c8cda2fbdf900c755cd1a13fc8992f6eb8ad5c432fef8f6fc6df5f43</originalsourceid><addsrcrecordid>eNp1kU1LHTEUhkOx1Kvton-gBNzUxWg-bjKTpYhVQXChrkMmH04kMxmTDHJX_vXm9loXgtmcwHnOw-G8APzE6ATXdzr4fIIpb9dfwKpW1hDGxB5YIYpEgzBv98FBzk8I4ZYS8g3sEyEQp5iuwOv9YKHxuSTfL8XHCUYH_VSSKssYkwpwVDrFeVCPNkMdU7JBlfp98WWAYwxWL0ElOA92imUz146aDPTjrHTJcE7xcYrZ5-qs0yEmq0uVapW0n-KovoOvToVsf7zVQ_Dw5-L-_Kq5ub28Pj-7aTRldN04ZzTvueG600YR1xsnENItY9pghanTnRDEcdt3yjC9psRZ1znuNDeOuTU9BL933rrR82JzkaPP2oagJhuXLAlinHYC8y169AF9ikua6naS1GujlgiypY53VL1Ozsk6OSc_qrSRGMltKrKmIv-lUtlfb8alH615J__HUIHTHfDig918bpJX13c75V82BJsw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2111072924</pqid></control><display><type>article</type><title>The distribution of intratumoral macrophages correlates with molecular phenotypes and impacts prognosis in colorectal carcinoma</title><source>Wiley</source><creator>Kim, Younghoon ; Wen, Xianyu ; Bae, Jeong M ; Kim, Jung H ; Cho, Nam‐Yun ; Kang, Gyeong H</creator><creatorcontrib>Kim, Younghoon ; Wen, Xianyu ; Bae, Jeong M ; Kim, Jung H ; Cho, Nam‐Yun ; Kang, Gyeong H</creatorcontrib><description><![CDATA[Aims
The role of tumour‐associated macrophages (TAMs) in colorectal cancer (CRC) remains elusive. In this study, we aimed to examine the correlation between TAMs, clinicopathological features, tumour‐infiltrating lymphocytes (TILs) and prognosis in CRC by the use of image analysis.
Methods and results
Immunohistochemical staining for CD68 and CD163 was performed as pan‐macrophage and M2‐macrophage markers, respectively. Each marker was analysed separately for intra‐epithelial and stromal area densities. All four macrophage densities showed a significant correlation with one another (P = 0.001). Intra‐epithelial CD68+ macrophage densities showed a correlation with pTNM stage (P = 0.008), microsatellite instability (MSI) (P < 0.001), CpG island methylator phenotype (CIMP) (P < 0.001) and TIL densities (P < 0.001). Intra‐epithelial CD163+ macrophage densities were associated with perineural invasion, MSI, CIMP and TIL densities (P < 0.001). Stromal CD68+ and CD163+ macrophage densities had a significant relationship with intra‐epithelial and stromal CD3+ (P = 0.001 and P < 0.001, respectively) and CD8+ (P < 0.001) T cells. High intra‐epithelial CD68+ macrophage density was associated with worse overall survival (HR = 1.386, 95% CI = 1.043–1.843, P = 0.025) and progression‐free survival (HR = 1.522, 95% CI = 1.146–2.020, P = 0.004). Intra‐epithelial CD68+ macrophage density was also an independent prognostic factor of the progression‐free survival (HR = 1.447, 95% CI = 1.076–1.947, P = 0.015) of CRC patients regardless of pTNM stage, lymphatic, venous, and perineural invasions and TIL densities.
Conclusion
Our results indicate that the density of intratumoural macrophages is a useful prognostic indicator for further stratifying T cell populations in CRC.]]></description><identifier>ISSN: 0309-0167</identifier><identifier>EISSN: 1365-2559</identifier><identifier>DOI: 10.1111/his.13674</identifier><identifier>PMID: 29906313</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Adult ; Aged ; CD163 antigen ; CD3 antigen ; CD8 antigen ; Colorectal carcinoma ; Colorectal Neoplasms - immunology ; Colorectal Neoplasms - mortality ; Colorectal Neoplasms - pathology ; computer‐assisted image analysis ; CpG islands ; Female ; Humans ; Image processing ; Kaplan-Meier Estimate ; Lymphocytes T ; Lymphocytes, Tumor-Infiltrating - immunology ; Macrophages ; Macrophages - immunology ; Male ; Medical prognosis ; Microsatellite instability ; Middle Aged ; Phenotype ; Phenotypes ; Prognosis ; Progression-Free Survival ; Proportional Hazards Models ; Tumors ; tumour‐infiltrating lymphocytes</subject><ispartof>Histopathology, 2018-10, Vol.73 (4), p.663-671</ispartof><rights>2018 John Wiley & Sons Ltd</rights><rights>2018 John Wiley & Sons Ltd.</rights><rights>Copyright © 2018 John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3534-ffdc6b6d6c8cda2fbdf900c755cd1a13fc8992f6eb8ad5c432fef8f6fc6df5f43</citedby><cites>FETCH-LOGICAL-c3534-ffdc6b6d6c8cda2fbdf900c755cd1a13fc8992f6eb8ad5c432fef8f6fc6df5f43</cites><orcidid>0000-0003-2380-6675</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29906313$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Younghoon</creatorcontrib><creatorcontrib>Wen, Xianyu</creatorcontrib><creatorcontrib>Bae, Jeong M</creatorcontrib><creatorcontrib>Kim, Jung H</creatorcontrib><creatorcontrib>Cho, Nam‐Yun</creatorcontrib><creatorcontrib>Kang, Gyeong H</creatorcontrib><title>The distribution of intratumoral macrophages correlates with molecular phenotypes and impacts prognosis in colorectal carcinoma</title><title>Histopathology</title><addtitle>Histopathology</addtitle><description><![CDATA[Aims
The role of tumour‐associated macrophages (TAMs) in colorectal cancer (CRC) remains elusive. In this study, we aimed to examine the correlation between TAMs, clinicopathological features, tumour‐infiltrating lymphocytes (TILs) and prognosis in CRC by the use of image analysis.
Methods and results
Immunohistochemical staining for CD68 and CD163 was performed as pan‐macrophage and M2‐macrophage markers, respectively. Each marker was analysed separately for intra‐epithelial and stromal area densities. All four macrophage densities showed a significant correlation with one another (P = 0.001). Intra‐epithelial CD68+ macrophage densities showed a correlation with pTNM stage (P = 0.008), microsatellite instability (MSI) (P < 0.001), CpG island methylator phenotype (CIMP) (P < 0.001) and TIL densities (P < 0.001). Intra‐epithelial CD163+ macrophage densities were associated with perineural invasion, MSI, CIMP and TIL densities (P < 0.001). Stromal CD68+ and CD163+ macrophage densities had a significant relationship with intra‐epithelial and stromal CD3+ (P = 0.001 and P < 0.001, respectively) and CD8+ (P < 0.001) T cells. High intra‐epithelial CD68+ macrophage density was associated with worse overall survival (HR = 1.386, 95% CI = 1.043–1.843, P = 0.025) and progression‐free survival (HR = 1.522, 95% CI = 1.146–2.020, P = 0.004). Intra‐epithelial CD68+ macrophage density was also an independent prognostic factor of the progression‐free survival (HR = 1.447, 95% CI = 1.076–1.947, P = 0.015) of CRC patients regardless of pTNM stage, lymphatic, venous, and perineural invasions and TIL densities.
Conclusion
Our results indicate that the density of intratumoural macrophages is a useful prognostic indicator for further stratifying T cell populations in CRC.]]></description><subject>Adult</subject><subject>Aged</subject><subject>CD163 antigen</subject><subject>CD3 antigen</subject><subject>CD8 antigen</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - immunology</subject><subject>Colorectal Neoplasms - mortality</subject><subject>Colorectal Neoplasms - pathology</subject><subject>computer‐assisted image analysis</subject><subject>CpG islands</subject><subject>Female</subject><subject>Humans</subject><subject>Image processing</subject><subject>Kaplan-Meier Estimate</subject><subject>Lymphocytes T</subject><subject>Lymphocytes, Tumor-Infiltrating - immunology</subject><subject>Macrophages</subject><subject>Macrophages - immunology</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Microsatellite instability</subject><subject>Middle Aged</subject><subject>Phenotype</subject><subject>Phenotypes</subject><subject>Prognosis</subject><subject>Progression-Free Survival</subject><subject>Proportional Hazards Models</subject><subject>Tumors</subject><subject>tumour‐infiltrating lymphocytes</subject><issn>0309-0167</issn><issn>1365-2559</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp1kU1LHTEUhkOx1Kvton-gBNzUxWg-bjKTpYhVQXChrkMmH04kMxmTDHJX_vXm9loXgtmcwHnOw-G8APzE6ATXdzr4fIIpb9dfwKpW1hDGxB5YIYpEgzBv98FBzk8I4ZYS8g3sEyEQp5iuwOv9YKHxuSTfL8XHCUYH_VSSKssYkwpwVDrFeVCPNkMdU7JBlfp98WWAYwxWL0ElOA92imUz146aDPTjrHTJcE7xcYrZ5-qs0yEmq0uVapW0n-KovoOvToVsf7zVQ_Dw5-L-_Kq5ub28Pj-7aTRldN04ZzTvueG600YR1xsnENItY9pghanTnRDEcdt3yjC9psRZ1znuNDeOuTU9BL933rrR82JzkaPP2oagJhuXLAlinHYC8y169AF9ikua6naS1GujlgiypY53VL1Ozsk6OSc_qrSRGMltKrKmIv-lUtlfb8alH615J__HUIHTHfDig918bpJX13c75V82BJsw</recordid><startdate>201810</startdate><enddate>201810</enddate><creator>Kim, Younghoon</creator><creator>Wen, Xianyu</creator><creator>Bae, Jeong M</creator><creator>Kim, Jung H</creator><creator>Cho, Nam‐Yun</creator><creator>Kang, Gyeong H</creator><general>Wiley Subscription Services, Inc</general><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>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/0000-0003-2380-6675</orcidid></search><sort><creationdate>201810</creationdate><title>The distribution of intratumoral macrophages correlates with molecular phenotypes and impacts prognosis in colorectal carcinoma</title><author>Kim, Younghoon ; Wen, Xianyu ; Bae, Jeong M ; Kim, Jung H ; Cho, Nam‐Yun ; Kang, Gyeong H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3534-ffdc6b6d6c8cda2fbdf900c755cd1a13fc8992f6eb8ad5c432fef8f6fc6df5f43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>Aged</topic><topic>CD163 antigen</topic><topic>CD3 antigen</topic><topic>CD8 antigen</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - immunology</topic><topic>Colorectal Neoplasms - mortality</topic><topic>Colorectal Neoplasms - pathology</topic><topic>computer‐assisted image analysis</topic><topic>CpG islands</topic><topic>Female</topic><topic>Humans</topic><topic>Image processing</topic><topic>Kaplan-Meier Estimate</topic><topic>Lymphocytes T</topic><topic>Lymphocytes, Tumor-Infiltrating - immunology</topic><topic>Macrophages</topic><topic>Macrophages - immunology</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Microsatellite instability</topic><topic>Middle Aged</topic><topic>Phenotype</topic><topic>Phenotypes</topic><topic>Prognosis</topic><topic>Progression-Free Survival</topic><topic>Proportional Hazards Models</topic><topic>Tumors</topic><topic>tumour‐infiltrating lymphocytes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Younghoon</creatorcontrib><creatorcontrib>Wen, Xianyu</creatorcontrib><creatorcontrib>Bae, Jeong M</creatorcontrib><creatorcontrib>Kim, Jung H</creatorcontrib><creatorcontrib>Cho, Nam‐Yun</creatorcontrib><creatorcontrib>Kang, Gyeong H</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><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>Kim, Younghoon</au><au>Wen, Xianyu</au><au>Bae, Jeong M</au><au>Kim, Jung H</au><au>Cho, Nam‐Yun</au><au>Kang, Gyeong H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The distribution of intratumoral macrophages correlates with molecular phenotypes and impacts prognosis in colorectal carcinoma</atitle><jtitle>Histopathology</jtitle><addtitle>Histopathology</addtitle><date>2018-10</date><risdate>2018</risdate><volume>73</volume><issue>4</issue><spage>663</spage><epage>671</epage><pages>663-671</pages><issn>0309-0167</issn><eissn>1365-2559</eissn><abstract><![CDATA[Aims
The role of tumour‐associated macrophages (TAMs) in colorectal cancer (CRC) remains elusive. In this study, we aimed to examine the correlation between TAMs, clinicopathological features, tumour‐infiltrating lymphocytes (TILs) and prognosis in CRC by the use of image analysis.
Methods and results
Immunohistochemical staining for CD68 and CD163 was performed as pan‐macrophage and M2‐macrophage markers, respectively. Each marker was analysed separately for intra‐epithelial and stromal area densities. All four macrophage densities showed a significant correlation with one another (P = 0.001). Intra‐epithelial CD68+ macrophage densities showed a correlation with pTNM stage (P = 0.008), microsatellite instability (MSI) (P < 0.001), CpG island methylator phenotype (CIMP) (P < 0.001) and TIL densities (P < 0.001). Intra‐epithelial CD163+ macrophage densities were associated with perineural invasion, MSI, CIMP and TIL densities (P < 0.001). Stromal CD68+ and CD163+ macrophage densities had a significant relationship with intra‐epithelial and stromal CD3+ (P = 0.001 and P < 0.001, respectively) and CD8+ (P < 0.001) T cells. High intra‐epithelial CD68+ macrophage density was associated with worse overall survival (HR = 1.386, 95% CI = 1.043–1.843, P = 0.025) and progression‐free survival (HR = 1.522, 95% CI = 1.146–2.020, P = 0.004). Intra‐epithelial CD68+ macrophage density was also an independent prognostic factor of the progression‐free survival (HR = 1.447, 95% CI = 1.076–1.947, P = 0.015) of CRC patients regardless of pTNM stage, lymphatic, venous, and perineural invasions and TIL densities.
Conclusion
Our results indicate that the density of intratumoural macrophages is a useful prognostic indicator for further stratifying T cell populations in CRC.]]></abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>29906313</pmid><doi>10.1111/his.13674</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-2380-6675</orcidid></addata></record> |
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| subjects | Adult Aged CD163 antigen CD3 antigen CD8 antigen Colorectal carcinoma Colorectal Neoplasms - immunology Colorectal Neoplasms - mortality Colorectal Neoplasms - pathology computer‐assisted image analysis CpG islands Female Humans Image processing Kaplan-Meier Estimate Lymphocytes T Lymphocytes, Tumor-Infiltrating - immunology Macrophages Macrophages - immunology Male Medical prognosis Microsatellite instability Middle Aged Phenotype Phenotypes Prognosis Progression-Free Survival Proportional Hazards Models Tumors tumour‐infiltrating lymphocytes |
| title | The distribution of intratumoral macrophages correlates with molecular phenotypes and impacts prognosis in colorectal carcinoma |
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