β2-microglobulin expression is associated with aggressive histology, activated tumor immune milieu, and outcome in colon carcinoma
Abstract Objectives We sought to assess the expression of human leukocyte antigen (HLA) proteins and β2-microglobulin (B2M) in tumor cells and the relationship with immune microenvironment and outcome in colorectal cancer (CRC). Methods A total of 953 CRC cases were evaluated by immunohistochemistry...
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| Veröffentlicht in: | American journal of clinical pathology 2024-11, Vol.162 (5), p.500-508 |
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| container_title | American journal of clinical pathology |
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| creator | Lee, Soo Hyun Pankaj, Amaya Rickelt, Steffen Ting, David Ferrone, Cristina Patil, Deepa T Yilmaz, Omer Berger, David Deshpande, Vikram Yilmaz, Osman |
| description | Abstract
Objectives
We sought to assess the expression of human leukocyte antigen (HLA) proteins and β2-microglobulin (B2M) in tumor cells and the relationship with immune microenvironment and outcome in colorectal cancer (CRC).
Methods
A total of 953 CRC cases were evaluated by immunohistochemistry for HLA class I, HLA class II, and B2M. The expression level of these biomarkers was correlated with clinicopathologic information, BRAF V600E and mismatch repair (MMR) proteins, and the quantitated expression levels of immune cells (CD8 and CD163) and immune regulatory proteins (FoxP3, programmed cell death 1 ligand 1 [PD-L1], and LAG3).
Results
We found that B2M-low tumors were statistically correlated with aggressive histologic features, including higher stage, higher grade, extramural venous invasion, perineural invasion, and distant metastasis. Expression of B2M was positively correlated (R2 = 0.3) and significantly associated with MMR-deficient tumors (P < .001); B2M-low tumors were also associated with an “immune cold”’ microenvironment, including a reduced number of immune cells (CD8 and CD163), reduced expression of immune regulatory proteins by immune cells (PD-L1, FoxP3, and LAG3), and reduced tumor cell expression of PD-L1. These B2M-low tumors correlated with lower disease-specific survival (P = .018), a finding that maintained significance only for the proficient MMR cohort (P = .037).
Conclusions
Our findings suggest that B2M expression may support predictive models for both outcome and checkpoint inhibitor therapy treatment response for colorectal adenocarcinoma. |
| doi_str_mv | 10.1093/ajcp/aqae066 |
| format | Article |
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Objectives
We sought to assess the expression of human leukocyte antigen (HLA) proteins and β2-microglobulin (B2M) in tumor cells and the relationship with immune microenvironment and outcome in colorectal cancer (CRC).
Methods
A total of 953 CRC cases were evaluated by immunohistochemistry for HLA class I, HLA class II, and B2M. The expression level of these biomarkers was correlated with clinicopathologic information, BRAF V600E and mismatch repair (MMR) proteins, and the quantitated expression levels of immune cells (CD8 and CD163) and immune regulatory proteins (FoxP3, programmed cell death 1 ligand 1 [PD-L1], and LAG3).
Results
We found that B2M-low tumors were statistically correlated with aggressive histologic features, including higher stage, higher grade, extramural venous invasion, perineural invasion, and distant metastasis. Expression of B2M was positively correlated (R2 = 0.3) and significantly associated with MMR-deficient tumors (P < .001); B2M-low tumors were also associated with an “immune cold”’ microenvironment, including a reduced number of immune cells (CD8 and CD163), reduced expression of immune regulatory proteins by immune cells (PD-L1, FoxP3, and LAG3), and reduced tumor cell expression of PD-L1. These B2M-low tumors correlated with lower disease-specific survival (P = .018), a finding that maintained significance only for the proficient MMR cohort (P = .037).
Conclusions
Our findings suggest that B2M expression may support predictive models for both outcome and checkpoint inhibitor therapy treatment response for colorectal adenocarcinoma.</description><identifier>ISSN: 0002-9173</identifier><identifier>ISSN: 1943-7722</identifier><identifier>EISSN: 1943-7722</identifier><identifier>DOI: 10.1093/ajcp/aqae066</identifier><identifier>PMID: 38869306</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Adenocarcinoma ; Adult ; Aged ; Aged, 80 and over ; Apoptosis ; beta 2-Microglobulin - metabolism ; Biomarkers, Tumor - metabolism ; CD163 antigen ; CD8 antigen ; Cell death ; Colonic Neoplasms - immunology ; Colonic Neoplasms - metabolism ; Colonic Neoplasms - mortality ; Colonic Neoplasms - pathology ; Colorectal carcinoma ; Female ; Foxp3 protein ; Histocompatibility antigen HLA ; Humans ; Immune checkpoint inhibitors ; Immunohistochemistry ; Male ; Metastases ; Microenvironments ; Middle Aged ; Mismatch repair ; PD-L1 protein ; Prediction models ; Prognosis ; Proteins ; Regulatory proteins ; Tumor cells ; Tumor Microenvironment - immunology ; Tumors ; β2 Microglobulin</subject><ispartof>American journal of clinical pathology, 2024-11, Vol.162 (5), p.500-508</ispartof><rights>The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. 2024</rights><rights>The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c238t-f2bcacf011bea15396c192343f6aebf37c5c812b13b166b6c096a02f083628033</cites><orcidid>0000-0001-9822-7112 ; 0000-0002-9622-357X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1583,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38869306$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Soo Hyun</creatorcontrib><creatorcontrib>Pankaj, Amaya</creatorcontrib><creatorcontrib>Rickelt, Steffen</creatorcontrib><creatorcontrib>Ting, David</creatorcontrib><creatorcontrib>Ferrone, Cristina</creatorcontrib><creatorcontrib>Patil, Deepa T</creatorcontrib><creatorcontrib>Yilmaz, Omer</creatorcontrib><creatorcontrib>Berger, David</creatorcontrib><creatorcontrib>Deshpande, Vikram</creatorcontrib><creatorcontrib>Yilmaz, Osman</creatorcontrib><title>β2-microglobulin expression is associated with aggressive histology, activated tumor immune milieu, and outcome in colon carcinoma</title><title>American journal of clinical pathology</title><addtitle>Am J Clin Pathol</addtitle><description>Abstract
Objectives
We sought to assess the expression of human leukocyte antigen (HLA) proteins and β2-microglobulin (B2M) in tumor cells and the relationship with immune microenvironment and outcome in colorectal cancer (CRC).
Methods
A total of 953 CRC cases were evaluated by immunohistochemistry for HLA class I, HLA class II, and B2M. The expression level of these biomarkers was correlated with clinicopathologic information, BRAF V600E and mismatch repair (MMR) proteins, and the quantitated expression levels of immune cells (CD8 and CD163) and immune regulatory proteins (FoxP3, programmed cell death 1 ligand 1 [PD-L1], and LAG3).
Results
We found that B2M-low tumors were statistically correlated with aggressive histologic features, including higher stage, higher grade, extramural venous invasion, perineural invasion, and distant metastasis. Expression of B2M was positively correlated (R2 = 0.3) and significantly associated with MMR-deficient tumors (P < .001); B2M-low tumors were also associated with an “immune cold”’ microenvironment, including a reduced number of immune cells (CD8 and CD163), reduced expression of immune regulatory proteins by immune cells (PD-L1, FoxP3, and LAG3), and reduced tumor cell expression of PD-L1. These B2M-low tumors correlated with lower disease-specific survival (P = .018), a finding that maintained significance only for the proficient MMR cohort (P = .037).
Conclusions
Our findings suggest that B2M expression may support predictive models for both outcome and checkpoint inhibitor therapy treatment response for colorectal adenocarcinoma.</description><subject>Adenocarcinoma</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Apoptosis</subject><subject>beta 2-Microglobulin - metabolism</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>CD163 antigen</subject><subject>CD8 antigen</subject><subject>Cell death</subject><subject>Colonic Neoplasms - immunology</subject><subject>Colonic Neoplasms - metabolism</subject><subject>Colonic Neoplasms - mortality</subject><subject>Colonic Neoplasms - pathology</subject><subject>Colorectal carcinoma</subject><subject>Female</subject><subject>Foxp3 protein</subject><subject>Histocompatibility antigen HLA</subject><subject>Humans</subject><subject>Immune checkpoint inhibitors</subject><subject>Immunohistochemistry</subject><subject>Male</subject><subject>Metastases</subject><subject>Microenvironments</subject><subject>Middle Aged</subject><subject>Mismatch repair</subject><subject>PD-L1 protein</subject><subject>Prediction models</subject><subject>Prognosis</subject><subject>Proteins</subject><subject>Regulatory proteins</subject><subject>Tumor cells</subject><subject>Tumor Microenvironment - immunology</subject><subject>Tumors</subject><subject>β2 Microglobulin</subject><issn>0002-9173</issn><issn>1943-7722</issn><issn>1943-7722</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kb1u2zAUhYkiQeO43ToHBDI0Q9Rc8iqUNAZGkxQwkCWdBYqmHBqiKJOi08x9oz5Inyn0TztkyEIO5-PhvecQ8oXBNwYVXsmVGq7kWmoQ4gOZsCrHrCg4PyITAOBZxQo8IachrAAYLyH_SE6wLEWFICbk998_PLNGebfsXBM701P9a_A6BON6agKVIThl5KgX9NmMT1Qulzt1o-mTCaPr3PLlkko1ms0OGqN1nhprY6-pNZ3RMcn9gro4Kmc1TT-o9Cqd0ivTOys_keNWdkF_PtxT8vP2--PsPps_3P2Y3cwzxbEcs5Y3SqoWGGu0ZNdYCcUqjjm2QuqmxUJdq5LxhmHDhGiEgkpI4C2UKNLeiFNysfcdvFtHHcbamqB018leuxjqFEhRsTwXeULP36ArF32fpqtxGyIgYJGoyz2V4gvB67YevLHSv9QM6m059bac-lBOws8OprGxevEf_tdGAr7uAReH961eAT_xm9U</recordid><startdate>20241104</startdate><enddate>20241104</enddate><creator>Lee, Soo Hyun</creator><creator>Pankaj, Amaya</creator><creator>Rickelt, Steffen</creator><creator>Ting, David</creator><creator>Ferrone, Cristina</creator><creator>Patil, Deepa T</creator><creator>Yilmaz, Omer</creator><creator>Berger, David</creator><creator>Deshpande, Vikram</creator><creator>Yilmaz, Osman</creator><general>Oxford University Press</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>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9822-7112</orcidid><orcidid>https://orcid.org/0000-0002-9622-357X</orcidid></search><sort><creationdate>20241104</creationdate><title>β2-microglobulin expression is associated with aggressive histology, activated tumor immune milieu, and outcome in colon carcinoma</title><author>Lee, Soo Hyun ; Pankaj, Amaya ; Rickelt, Steffen ; Ting, David ; Ferrone, Cristina ; Patil, Deepa T ; Yilmaz, Omer ; Berger, David ; Deshpande, Vikram ; Yilmaz, Osman</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c238t-f2bcacf011bea15396c192343f6aebf37c5c812b13b166b6c096a02f083628033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adenocarcinoma</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Apoptosis</topic><topic>beta 2-Microglobulin - metabolism</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>CD163 antigen</topic><topic>CD8 antigen</topic><topic>Cell death</topic><topic>Colonic Neoplasms - immunology</topic><topic>Colonic Neoplasms - metabolism</topic><topic>Colonic Neoplasms - mortality</topic><topic>Colonic Neoplasms - pathology</topic><topic>Colorectal carcinoma</topic><topic>Female</topic><topic>Foxp3 protein</topic><topic>Histocompatibility antigen HLA</topic><topic>Humans</topic><topic>Immune checkpoint inhibitors</topic><topic>Immunohistochemistry</topic><topic>Male</topic><topic>Metastases</topic><topic>Microenvironments</topic><topic>Middle Aged</topic><topic>Mismatch repair</topic><topic>PD-L1 protein</topic><topic>Prediction models</topic><topic>Prognosis</topic><topic>Proteins</topic><topic>Regulatory proteins</topic><topic>Tumor cells</topic><topic>Tumor Microenvironment - immunology</topic><topic>Tumors</topic><topic>β2 Microglobulin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Soo Hyun</creatorcontrib><creatorcontrib>Pankaj, Amaya</creatorcontrib><creatorcontrib>Rickelt, Steffen</creatorcontrib><creatorcontrib>Ting, David</creatorcontrib><creatorcontrib>Ferrone, Cristina</creatorcontrib><creatorcontrib>Patil, Deepa T</creatorcontrib><creatorcontrib>Yilmaz, Omer</creatorcontrib><creatorcontrib>Berger, David</creatorcontrib><creatorcontrib>Deshpande, Vikram</creatorcontrib><creatorcontrib>Yilmaz, Osman</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of clinical pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Soo Hyun</au><au>Pankaj, Amaya</au><au>Rickelt, Steffen</au><au>Ting, David</au><au>Ferrone, Cristina</au><au>Patil, Deepa T</au><au>Yilmaz, Omer</au><au>Berger, David</au><au>Deshpande, Vikram</au><au>Yilmaz, Osman</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>β2-microglobulin expression is associated with aggressive histology, activated tumor immune milieu, and outcome in colon carcinoma</atitle><jtitle>American journal of clinical pathology</jtitle><addtitle>Am J Clin Pathol</addtitle><date>2024-11-04</date><risdate>2024</risdate><volume>162</volume><issue>5</issue><spage>500</spage><epage>508</epage><pages>500-508</pages><issn>0002-9173</issn><issn>1943-7722</issn><eissn>1943-7722</eissn><abstract>Abstract
Objectives
We sought to assess the expression of human leukocyte antigen (HLA) proteins and β2-microglobulin (B2M) in tumor cells and the relationship with immune microenvironment and outcome in colorectal cancer (CRC).
Methods
A total of 953 CRC cases were evaluated by immunohistochemistry for HLA class I, HLA class II, and B2M. The expression level of these biomarkers was correlated with clinicopathologic information, BRAF V600E and mismatch repair (MMR) proteins, and the quantitated expression levels of immune cells (CD8 and CD163) and immune regulatory proteins (FoxP3, programmed cell death 1 ligand 1 [PD-L1], and LAG3).
Results
We found that B2M-low tumors were statistically correlated with aggressive histologic features, including higher stage, higher grade, extramural venous invasion, perineural invasion, and distant metastasis. Expression of B2M was positively correlated (R2 = 0.3) and significantly associated with MMR-deficient tumors (P < .001); B2M-low tumors were also associated with an “immune cold”’ microenvironment, including a reduced number of immune cells (CD8 and CD163), reduced expression of immune regulatory proteins by immune cells (PD-L1, FoxP3, and LAG3), and reduced tumor cell expression of PD-L1. These B2M-low tumors correlated with lower disease-specific survival (P = .018), a finding that maintained significance only for the proficient MMR cohort (P = .037).
Conclusions
Our findings suggest that B2M expression may support predictive models for both outcome and checkpoint inhibitor therapy treatment response for colorectal adenocarcinoma.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>38869306</pmid><doi>10.1093/ajcp/aqae066</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-9822-7112</orcidid><orcidid>https://orcid.org/0000-0002-9622-357X</orcidid></addata></record> |
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| issn | 0002-9173 1943-7722 1943-7722 |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current) |
| subjects | Adenocarcinoma Adult Aged Aged, 80 and over Apoptosis beta 2-Microglobulin - metabolism Biomarkers, Tumor - metabolism CD163 antigen CD8 antigen Cell death Colonic Neoplasms - immunology Colonic Neoplasms - metabolism Colonic Neoplasms - mortality Colonic Neoplasms - pathology Colorectal carcinoma Female Foxp3 protein Histocompatibility antigen HLA Humans Immune checkpoint inhibitors Immunohistochemistry Male Metastases Microenvironments Middle Aged Mismatch repair PD-L1 protein Prediction models Prognosis Proteins Regulatory proteins Tumor cells Tumor Microenvironment - immunology Tumors β2 Microglobulin |
| title | β2-microglobulin expression is associated with aggressive histology, activated tumor immune milieu, and outcome in colon carcinoma |
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