Association between local immune cell infiltration, mismatch repair status and systemic inflammatory response in colorectal cancer
BACKGROUND: Systemic inflammatory response in colorectal cancer (CRC) has been established as a prognostic factor for impaired cancer-specific survival, predominantly in patients with right-sided tumors. On the other hand, defective mismatch repair (dMMR) tumors, primarily located in the right colon...
Published in: | Journal of Translational Medicine |
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Main Authors: | , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
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Umeå universitet, Kirurgi
2020
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Online Access: | http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-170488 https://doi.org/10.1186/s12967-020-02336-6 |
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ftumeauniv:oai:DiVA.org:umu-170488 |
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Open Polar |
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Umeå University: Publications (DiVA) |
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ftumeauniv |
language |
English |
topic |
Colorectal cancer Local immune response Miscrosatellite instability Mismatch repair Systematic inflammatory response Cancer and Oncology Cancer och onkologi |
spellingShingle |
Colorectal cancer Local immune response Miscrosatellite instability Mismatch repair Systematic inflammatory response Cancer and Oncology Cancer och onkologi Gunnarsson, Ulf Strigård, Karin Edin, Sofia Gkekas, Ioannis Mustonen, Harri Kaprio, Tuomas Böckelman, Camilla Hagström, Jaana Palmqvist, Richard Haglund, Caj Association between local immune cell infiltration, mismatch repair status and systemic inflammatory response in colorectal cancer |
topic_facet |
Colorectal cancer Local immune response Miscrosatellite instability Mismatch repair Systematic inflammatory response Cancer and Oncology Cancer och onkologi |
description |
BACKGROUND: Systemic inflammatory response in colorectal cancer (CRC) has been established as a prognostic factor for impaired cancer-specific survival, predominantly in patients with right-sided tumors. On the other hand, defective mismatch repair (dMMR) tumors, primarily located in the right colon, are known to have favorable survival and dense local immune infiltration. The aim of this study was to see if there is any form of relationship between these seemingly diverse entities. METHODS: Complete clinical and long-term survival data were retrieved for 316 CRC patients operated at Helsinki University Hospital between the years 1998 and 2003. Tissue microarrays were prepared from surgical specimens and further processed and analyzed for local immune cell infiltration using multispectral imaging with a Vectra quantitative pathology imaging system and Inform software. Multiplex immunohistochemistry was applied using antibodies against CD66b, CD8, CD20, FoxP3, CD68 and pan-Cytokeratin. After exclusions, data on immune infiltration were available for 275 patients. Mismatch repair status was determined by immunohistochemistry. RESULTS: CRP was seen to be an independent predictor of cancer-specific survival but not overall survival in uni- and multivariable (HR 1.01 (1.00-1.02); p = 0.028) analyses of non-irradiated patients. There was no significant difference in CRP according to mismatch repair status, but all cases (n = 10) with CRP ≥ 75 mg/l had proficient mismatch repair (pMMR). There was a significant negative correlation between intratumor stromal infiltration by T-regulatory FOXP3+ cells and CRP (p = 0.006). There was significantly lower intratumor stromal infiltration by FOXP3+ cells (p = 0.043) in the right colon compared to the rectum, but no significant difference in CRP (p = 0.44). CRP was not a predictor of overall survival (HR 0.99, 95% CI 0.98-1.01) nor cancer-specific survival in irradiated patients (HR 0.94, 95% CI 0.94-1.02). CONCLUSIONS: There was a significant negative relationship between SIR, defined as an elevated CRP, and intratumor stromal infiltration by T-regulatory FOXP3+ cells. This and the fact that all cases with a CRP > 75 mg/l had pMMR suggests that SIR and dMMR are independent entities in CRC. Indeed, the general lack of difference in CRP between cases with dMMR and pMMR may be evidence of overlap in cases with a less pronounced SIR. This investigation was supported by grants from the Cancer Research Foundation in Northern Sweden (Dnr LP 16-2131), the Nordic Cancer Union, the Sigrid Jusélius Foundation in Finland and the Finnish Cancer Foundation. |
format |
Article in Journal/Newspaper |
author |
Gunnarsson, Ulf Strigård, Karin Edin, Sofia Gkekas, Ioannis Mustonen, Harri Kaprio, Tuomas Böckelman, Camilla Hagström, Jaana Palmqvist, Richard Haglund, Caj |
author_facet |
Gunnarsson, Ulf Strigård, Karin Edin, Sofia Gkekas, Ioannis Mustonen, Harri Kaprio, Tuomas Böckelman, Camilla Hagström, Jaana Palmqvist, Richard Haglund, Caj |
author_sort |
Gunnarsson, Ulf |
title |
Association between local immune cell infiltration, mismatch repair status and systemic inflammatory response in colorectal cancer |
title_short |
Association between local immune cell infiltration, mismatch repair status and systemic inflammatory response in colorectal cancer |
title_full |
Association between local immune cell infiltration, mismatch repair status and systemic inflammatory response in colorectal cancer |
title_fullStr |
Association between local immune cell infiltration, mismatch repair status and systemic inflammatory response in colorectal cancer |
title_full_unstemmed |
Association between local immune cell infiltration, mismatch repair status and systemic inflammatory response in colorectal cancer |
title_sort |
association between local immune cell infiltration, mismatch repair status and systemic inflammatory response in colorectal cancer |
publisher |
Umeå universitet, Kirurgi |
publishDate |
2020 |
url |
http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-170488 https://doi.org/10.1186/s12967-020-02336-6 |
long_lat |
ENVELOPE(-64.233,-64.233,-64.250,-64.250) |
geographic |
Sigrid |
geographic_facet |
Sigrid |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_relation |
Journal of Translational Medicine, 1479-5876, 2020, 18, http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-170488 doi:10.1186/s12967-020-02336-6 PMID 32316975 ISI:000529499500003 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.1186/s12967-020-02336-6 |
container_title |
Journal of Translational Medicine |
container_volume |
18 |
container_issue |
1 |
_version_ |
1766148095807062016 |
spelling |
ftumeauniv:oai:DiVA.org:umu-170488 2023-05-15T17:45:14+02:00 Association between local immune cell infiltration, mismatch repair status and systemic inflammatory response in colorectal cancer Gunnarsson, Ulf Strigård, Karin Edin, Sofia Gkekas, Ioannis Mustonen, Harri Kaprio, Tuomas Böckelman, Camilla Hagström, Jaana Palmqvist, Richard Haglund, Caj 2020 application/pdf http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-170488 https://doi.org/10.1186/s12967-020-02336-6 eng eng Umeå universitet, Kirurgi Umeå universitet, Patologi Department of Surgery, University of Helsinki and Helsinki University Hospital, 00114, Helsinki, Finland. Translational Cancer Medicine Research Program, Faculty of Medicine, University of Helsinki, 00014, Helsinki, Finland. Translational Cancer Medicine Research Program, Faculty of Medicine, University of Helsinki, 00014, Helsinki, Finland. Department of Pathology, University of Helsinki and Helsinki University Hospital, 00014, Helsinki, Finland. Journal of Translational Medicine, 1479-5876, 2020, 18, http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-170488 doi:10.1186/s12967-020-02336-6 PMID 32316975 ISI:000529499500003 info:eu-repo/semantics/openAccess Colorectal cancer Local immune response Miscrosatellite instability Mismatch repair Systematic inflammatory response Cancer and Oncology Cancer och onkologi Article in journal info:eu-repo/semantics/article text 2020 ftumeauniv https://doi.org/10.1186/s12967-020-02336-6 2022-05-01T08:21:16Z BACKGROUND: Systemic inflammatory response in colorectal cancer (CRC) has been established as a prognostic factor for impaired cancer-specific survival, predominantly in patients with right-sided tumors. On the other hand, defective mismatch repair (dMMR) tumors, primarily located in the right colon, are known to have favorable survival and dense local immune infiltration. The aim of this study was to see if there is any form of relationship between these seemingly diverse entities. METHODS: Complete clinical and long-term survival data were retrieved for 316 CRC patients operated at Helsinki University Hospital between the years 1998 and 2003. Tissue microarrays were prepared from surgical specimens and further processed and analyzed for local immune cell infiltration using multispectral imaging with a Vectra quantitative pathology imaging system and Inform software. Multiplex immunohistochemistry was applied using antibodies against CD66b, CD8, CD20, FoxP3, CD68 and pan-Cytokeratin. After exclusions, data on immune infiltration were available for 275 patients. Mismatch repair status was determined by immunohistochemistry. RESULTS: CRP was seen to be an independent predictor of cancer-specific survival but not overall survival in uni- and multivariable (HR 1.01 (1.00-1.02); p = 0.028) analyses of non-irradiated patients. There was no significant difference in CRP according to mismatch repair status, but all cases (n = 10) with CRP ≥ 75 mg/l had proficient mismatch repair (pMMR). There was a significant negative correlation between intratumor stromal infiltration by T-regulatory FOXP3+ cells and CRP (p = 0.006). There was significantly lower intratumor stromal infiltration by FOXP3+ cells (p = 0.043) in the right colon compared to the rectum, but no significant difference in CRP (p = 0.44). CRP was not a predictor of overall survival (HR 0.99, 95% CI 0.98-1.01) nor cancer-specific survival in irradiated patients (HR 0.94, 95% CI 0.94-1.02). CONCLUSIONS: There was a significant negative relationship between SIR, defined as an elevated CRP, and intratumor stromal infiltration by T-regulatory FOXP3+ cells. This and the fact that all cases with a CRP > 75 mg/l had pMMR suggests that SIR and dMMR are independent entities in CRC. Indeed, the general lack of difference in CRP between cases with dMMR and pMMR may be evidence of overlap in cases with a less pronounced SIR. This investigation was supported by grants from the Cancer Research Foundation in Northern Sweden (Dnr LP 16-2131), the Nordic Cancer Union, the Sigrid Jusélius Foundation in Finland and the Finnish Cancer Foundation. Article in Journal/Newspaper Northern Sweden Umeå University: Publications (DiVA) Sigrid ENVELOPE(-64.233,-64.233,-64.250,-64.250) Journal of Translational Medicine 18 1 |