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Abstract
Aims The immune checkpoint marker, Programmed cell death-ligand 1 (PD-L1), is expressed by both cancer epithelial cells and tumour-infiltrating immune cells (TICs) thus constituting a potential target for immunotherapy. This is of particular interest in triple negative breast cancer. In this study, we assessed the prognostic value of PD-L1 expression in tumour epithelial cells and TICs in a series of patients with breast cancer with long-term follow-up, and associations between PD-L1 expression and histopathological type and grade, proliferation and molecular subtype.
Methods Using immunohistochemistry for PD-L1 in tissue microarrays, we assessed PD-L1 expression in 821 tumours. Expression of PD-L1 was assessed separately in the epithelial and stromal compartments and classified as <1%, ≥1% to <10% or ≥10% positive staining cells. We correlated PD-L1 expression in tumour epithelial cells and TICs with tumour characteristics using Pearson’s χ2 test, and prognosis by cumulative incidence of death from breast cancer and Cox regression analyses.
Results We found membranous staining in ≥1% of tumour epithelial cells in 53/821 cases (6.5%). Of these, 21 (2.6%) were ≥10%. Among TICs, staining (≥1%) was seen in 144/821 cases (17.6%). Of these, 62 were ≥10% (7.6%). PD-L1 was associated with high histopathological grade and proliferation, and the medullary and metaplastic patterns. In TICs, PD-L1 ≥1% found in 22/34 (34.4%) human epidermal growth factor receptor 2 type and 29/58 (50%) basal phenotype. An independent association between PD-L1 expression and prognosis was not observed.
Conclusions PD-L1 is expressed more frequently in TICs than tumour epithelial cells. Expression in TICs is associated with aggressive tumour characteristics and non-luminal tumours but not with prognosis.
- breast cancer
- immunohistochemistry
- biomarkers
- tumor
Data availability statement
Data are available upon reasonable request. The data included in the current study are not publicly available due to reasons of sensitivity and limitations imposed in the conditions for approval by the Ethics Committee but are available from the corresponding author on reasonable request.
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Data availability statement
Data are available upon reasonable request. The data included in the current study are not publicly available due to reasons of sensitivity and limitations imposed in the conditions for approval by the Ethics Committee but are available from the corresponding author on reasonable request.
Footnotes
Handling editor L C Collins.
Contributors SAS contributed to histologic analyses; statistical analyses and main author of the manuscript. AHS contributed to statistical analyses; review and approval the manuscript. BY contributed to laboratory methods; staining optimalisation; review and approval the manuscript. MJE contributed to review and approval the manuscript. AMB contributed to design of the study; histologic analyses; writing, review and approval the manuscript. Author acting as guarantor: AMB
Funding Liaison Committee between the Central Norway Regional Health Authority (RHA) and the Norwegian University of Science and Technology (NTNU).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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