The prognostic significance of immune microenvironment in breast ductal carcinoma in situ

Toss, Michael S; Abidi, Asima; Lesche, Dorothea; Joseph, Chitra; Mahale, Sakshi; Saunders, Hugo; Kader, Tanjina; Miligy, Islam M; Green, Andrew R.; Gorringe, Kylie L; Rakha, Emad A

Abstract

Background

The role of different subtypes of tumour infiltrating lymphocytes (TILs) in breast ductal carcinoma in situ (DCIS) is still poorly defined. This study aimed to assess the prognostic significance of B and T lymphocytes and immune checkpoint proteins expression in DCIS.

Methods

A well characterised DCIS cohort (n = 700) with long-term follow-up comprising pure DCIS (n = 508) and DCIS mixed with invasive carcinoma (IBC; n = 192) were stained immunohistochemically for CD20, CD3, CD4, CD8, FOXP3, PD1 and PDL1. Copy number variation and TP53 mutation status were assessed in a subset of cases (n = 58).

Results

CD3+ lymphocytes were the predominant cell subtype in the pure DCIS cohort, while FOXP3 showed the lowest levels. PDL1 expression was mainly seen in the stromal TILs. Higher abundance of TILs subtypes was associated with higher tumour grade, hormone receptor negativity and HER2 positivity. Mutant TP53 variants were associated with higher levels of stromal CD3+, CD4+ and FOXP3+ cells. DCIS coexisting with invasive carcinoma harboured denser stromal infiltrates of all immune cells and checkpoint proteins apart from CD4+ cells. Stromal PD1 was the most differentially expressed protein between DCIS and invasive carcinoma (Z = 5.8, p 

Citation

Toss, M. S., Abidi, A., Lesche, D., Joseph, C., Mahale, S., Saunders, H., Kader, T., Miligy, I. M., Green, A. R., Gorringe, K. L., & Rakha, E. A. (2020). The prognostic significance of immune microenvironment in breast ductal carcinoma in situ. British Journal of Cancer, 122, 1496–1506. https://doi.org/10.1038/s41416-020-0797-7

• Journal Article Type: Article
• Acceptance Date: Feb 6, 2020
• Online Publication Date: Mar 17, 2020
• Publication Date: May 12, 2020
• Deposit Date: Feb 17, 2020
• Publicly Available Date: Sep 18, 2020
• Journal: British Journal of Cancer
• Print ISSN: 0007-0920
• Electronic ISSN: 1532-1827
• Publisher: Cancer Research UK
• Peer Reviewed: Peer Reviewed
• Volume: 122
• Pages: 1496–1506
• DOI: https://doi.org/10.1038/s41416-020-0797-7
• Keywords: immune cell markers; PD1; PDL1; TILs; DCIS; prognostic; cancer research; oncology
• Public URL: https://nottingham-repository.worktribe.com/output/3978866
• Publisher URL: https://www.nature.com/articles/s41416-020-0797-7
• Additional Information: Received: 15 October 2019; Revised: 7 February 2020; Accepted: 26 February 2020; First Online: 17 March 2020; : This work obtained ethics approval by the North West – Greater Manchester Central Research Ethics Committee under the title; Nottingham Health Science Biobank (NHSB), reference number 15/NW/0685. All patients included in this study were consented to participate in the study and to use their materials in research. All samples from Nottingham used in this study were pseudo-anonymised and stored in compliance with the UK Human Tissue Act. The study was performed in accordance with the Declaration of Helsinki.; : The authors confirm the data that has been used in this work is available on reasonable request.; : The authors declare no competing interests.; : This research was supported and funded by the Egyptian Ministry of Higher Education and Scientific Research. This research was supported by the Peter MacCallum Cancer Foundation and by the National Breast Cancer Foundations (IIRS-18-051).