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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Main Authors: 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
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-02-01
Series:Frontiers in Immunology
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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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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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