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Heterogeneity of Tumour Infiltrating Lymphocytes (TILs) in breast cancer and its prognostic significance

Althobiti, Maryam; Aleskandarany, Mohammed A.; Joseph, Chitra; Toss, Michael; Mongan, Nigel; Diez-Rodriguez, Maria; Nolan, Christopher C.; Ashankyty, Ibraheem; Ellis, Ian O.; Green, Andrew R.; Rakha, Emad A.


Maryam Althobiti

Mohammed A. Aleskandarany

Michael Toss

Maria Diez-Rodriguez

Christopher C. Nolan

Ibraheem Ashankyty

Professor of Breast Cancer Pathology


Background: Tumour-infiltrating lymphocytes (TILs) in breast cancer (BC) confer prognostic and predictive information. This study aims to assess the spatial and temporal heterogeneity of TILs in BC and its relationship with immune cell subtypes.
Method: Immunohistochemically-defined immune cell subtypes; T-cell markers (CD3, CD8, and FOXP3), B-cell marker (CD20) and histiocytic marker (CD68) were evaluated in a large series (n=1,165) of invasive BC. A subset of full-face haematoxylin and eosin (H&E) stained slides were examined for TILs heterogeneity within primary tumours and the corresponding local recurrent carcinomas to report on spatial and temporal TILs heterogeneity. H&E stained sections from multiple tumour blocks (3-4 blocks per case) representing different tumour areas were evaluated to assess TILS inter-slide heterogeneity as well as intra-slide heterogeneity.
Both average (AV-TILs) and hotspot (HS-TILs) stromal TILs were assessed.
Results: AV-TILs showed association with all immune cell subtypes however; the main component were CD3+ cells (mean number = 55) whereas CD20+cells comprised the least component (the mean number = 13). There was no significant statistical difference between TILs across tumour blocks of the same case (p=0.251 for AV-TILs and p=0.162 for HS-TILs). Triple negative breast cancer (TNBC) showed higher TILs compared with other BC subtypes


Althobiti, M., Aleskandarany, M. A., Joseph, C., Toss, M., Mongan, N., Diez-Rodriguez, M., …Rakha, E. A. (2018). Heterogeneity of Tumour Infiltrating Lymphocytes (TILs) in breast cancer and its prognostic significance. Histopathology, 73(6), 887-896. doi:10.1111/his.13695

Journal Article Type Article
Acceptance Date Jun 25, 2018
Online Publication Date Jun 27, 2018
Publication Date Dec 1, 2018
Deposit Date Jun 28, 2018
Publicly Available Date Jun 28, 2019
Journal Histopathology
Print ISSN 0309-0167
Electronic ISSN 0309-0167
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 73
Issue 6
Pages 887-896
Keywords breast cancer, TILs, outcome, heterogeneity
Public URL
Publisher URL
Copyright Statement Copyright information regarding this work can be found at the following address:
Additional Information This is the peer reviewed version of the following article: Heterogeneity of Tumour Infiltrating Lymphocytes (TILs) in Breast Cancer and its prognostic significance, Maryam Althobiti, Mohammed A Aleskandarany, Chitra Joseph, Michael Toss, Nigel Mongan, Maria Diez‐Rodriguez, Christopher C Nolan, Ibraheem Ashankyty, Ian O Ellis, Andrew R Green, Emad A Rakha, Histopathology, which has been published in final form at doi:10.1111/his.13695. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.


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