Assessing Tumor-Infiltrating Lymphocytes in Breast Cancer: A Proposal for Combining Immunohistochemistry and Gene Expression Analysis to Refine Scoring
Scoring of tumor-infiltrating lymphocytes (TILs) in breast cancer specimens has gained increasing attention, as TILs have prognostic and predictive value in HER2+ and triple-negative breast cancer. We evaluated the intra- and interrater variability when scoring TILs by visual inspection of hematoxyl...
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Frontiers Media S.A.
2022-02-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.794175/full |
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author | Hanne Locy Stefaan Verhulst Wilfried Cools Wim Waelput Stefanie Brock Louise Cras Ann Schiettecatte Jan Jonckheere Leo A. van Grunsven Marian Vanhoeij Kris Thielemans Karine Breckpot |
author_facet | Hanne Locy Stefaan Verhulst Wilfried Cools Wim Waelput Stefanie Brock Louise Cras Ann Schiettecatte Jan Jonckheere Leo A. van Grunsven Marian Vanhoeij Kris Thielemans Karine Breckpot |
author_sort | Hanne Locy |
collection | DOAJ |
description | Scoring of tumor-infiltrating lymphocytes (TILs) in breast cancer specimens has gained increasing attention, as TILs have prognostic and predictive value in HER2+ and triple-negative breast cancer. We evaluated the intra- and interrater variability when scoring TILs by visual inspection of hematoxylin and eosin-stained tissue sections. We further addressed whether immunohistochemical staining of these sections for immune cell surface markers CD45, CD3, CD4, and CD8 and combination with nanoString nCounter® gene expression analysis could refine TIL scoring. Formalin-fixed paraffin-embedded and fresh-frozen core needle biopsies of 12 female and treatment-naive breast cancer patients were included. Scoring of TILs was performed twice by three independent pathologists with a washout period of 3 days. Increasing intra- and interrater variability was observed with higher TIL numbers. The highest reproducibility was observed on tissue sections stained for CD3 and CD8. The latter TIL scores correlated well with the TIL scores obtained through nanoString nCounter® gene expression analysis. Gene expression analysis also revealed 104 and 62 genes that are positively and negatively related to both TIL scores. In conclusion, integration of immunohistochemistry and gene expression analysis is a valuable strategy to refine TIL scoring in breast tumors. |
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issn | 1664-3224 |
language | English |
last_indexed | 2024-12-23T23:07:28Z |
publishDate | 2022-02-01 |
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series | Frontiers in Immunology |
spelling | doaj.art-cbe7f728bd8a400ab71b04bfde52aa702022-12-21T17:26:45ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-02-011310.3389/fimmu.2022.794175794175Assessing Tumor-Infiltrating Lymphocytes in Breast Cancer: A Proposal for Combining Immunohistochemistry and Gene Expression Analysis to Refine ScoringHanne Locy0Stefaan Verhulst1Wilfried Cools2Wim Waelput3Stefanie Brock4Louise Cras5Ann Schiettecatte6Jan Jonckheere7Leo A. van Grunsven8Marian Vanhoeij9Kris Thielemans10Karine Breckpot11Laboratory for Molecular and Cellular Therapy, Department of Biomedical Sciences (BMWE), Vrije Universiteit Brussel (VUB), Brussels, BelgiumLiver Cell Biology Research Group, BMWE, VUB, Brussels, BelgiumInterfaculty Center Data processing and Statistics, VUB, Brussels, BelgiumDepartment of Anatomo-Pathology, Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, BelgiumDepartment of Anatomo-Pathology, Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, BelgiumDepartment of Anatomo-Pathology, Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, BelgiumDepartment of Radiology, UZ Brussel, Brussels, BelgiumDepartment of Radiology, UZ Brussel, Brussels, BelgiumLiver Cell Biology Research Group, BMWE, VUB, Brussels, BelgiumDepartment of Surgery, UZ Brussel, Brussels, BelgiumLaboratory for Molecular and Cellular Therapy, Department of Biomedical Sciences (BMWE), Vrije Universiteit Brussel (VUB), Brussels, BelgiumLaboratory for Molecular and Cellular Therapy, Department of Biomedical Sciences (BMWE), Vrije Universiteit Brussel (VUB), Brussels, BelgiumScoring of tumor-infiltrating lymphocytes (TILs) in breast cancer specimens has gained increasing attention, as TILs have prognostic and predictive value in HER2+ and triple-negative breast cancer. We evaluated the intra- and interrater variability when scoring TILs by visual inspection of hematoxylin and eosin-stained tissue sections. We further addressed whether immunohistochemical staining of these sections for immune cell surface markers CD45, CD3, CD4, and CD8 and combination with nanoString nCounter® gene expression analysis could refine TIL scoring. Formalin-fixed paraffin-embedded and fresh-frozen core needle biopsies of 12 female and treatment-naive breast cancer patients were included. Scoring of TILs was performed twice by three independent pathologists with a washout period of 3 days. Increasing intra- and interrater variability was observed with higher TIL numbers. The highest reproducibility was observed on tissue sections stained for CD3 and CD8. The latter TIL scores correlated well with the TIL scores obtained through nanoString nCounter® gene expression analysis. Gene expression analysis also revealed 104 and 62 genes that are positively and negatively related to both TIL scores. In conclusion, integration of immunohistochemistry and gene expression analysis is a valuable strategy to refine TIL scoring in breast tumors.https://www.frontiersin.org/articles/10.3389/fimmu.2022.794175/fullbreast cancerimmunohistochemistrygene expression profilingtumor-infiltrating lymphocyteimmunotherapy targets |
spellingShingle | Hanne Locy Stefaan Verhulst Wilfried Cools Wim Waelput Stefanie Brock Louise Cras Ann Schiettecatte Jan Jonckheere Leo A. van Grunsven Marian Vanhoeij Kris Thielemans Karine Breckpot Assessing Tumor-Infiltrating Lymphocytes in Breast Cancer: A Proposal for Combining Immunohistochemistry and Gene Expression Analysis to Refine Scoring Frontiers in Immunology breast cancer immunohistochemistry gene expression profiling tumor-infiltrating lymphocyte immunotherapy targets |
title | Assessing Tumor-Infiltrating Lymphocytes in Breast Cancer: A Proposal for Combining Immunohistochemistry and Gene Expression Analysis to Refine Scoring |
title_full | Assessing Tumor-Infiltrating Lymphocytes in Breast Cancer: A Proposal for Combining Immunohistochemistry and Gene Expression Analysis to Refine Scoring |
title_fullStr | Assessing Tumor-Infiltrating Lymphocytes in Breast Cancer: A Proposal for Combining Immunohistochemistry and Gene Expression Analysis to Refine Scoring |
title_full_unstemmed | Assessing Tumor-Infiltrating Lymphocytes in Breast Cancer: A Proposal for Combining Immunohistochemistry and Gene Expression Analysis to Refine Scoring |
title_short | Assessing Tumor-Infiltrating Lymphocytes in Breast Cancer: A Proposal for Combining Immunohistochemistry and Gene Expression Analysis to Refine Scoring |
title_sort | assessing tumor infiltrating lymphocytes in breast cancer a proposal for combining immunohistochemistry and gene expression analysis to refine scoring |
topic | breast cancer immunohistochemistry gene expression profiling tumor-infiltrating lymphocyte immunotherapy targets |
url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.794175/full |
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