Clinicopathological significance of lipocalin 2 nuclear expression in invasive breast cancer

Kurozumi, Sasagu; Alsaeed, Sami; Orah, Nnamdi; Miligy, Islam M.; Joseph, Chitra; Aljohani, Abrar; Toss, Michael S; Fujii, Takaaki; Shirabe, Ken; Green, Andrew R; Aleskandarany, Mohammed A; Rakha, Emad A

Abstract

PURPOSE: The epithelial–mesenchymal transition (EMT) plays a key role in breast cancer progression and metastasis. Lipocalin 2 (LCN2) is involved in the regulation of EMT. The aim of this study was to investigate the clinicopathological significance of LCN2 expression in breast cancer.

METHODS: The expression of LCN2 protein was immunohistochemically assessed in two well-characterised annotated cohorts of breast cancer (discovery cohort, n = 612; validation cohort, n = 1,363). The relationship of LCN2 expression and subcellular location with the clinicopathological factors and outcomes of patients was analysed.

RESULTS: Absent or reduced nuclear LCN2 expression was associated with features of aggressive behaviour, including high histological grade, high Nottingham Prognostic Index, high Ki67 labelling index, hormone receptor negativity and human epidermal growth factor receptor 2 positivity. The high cytoplasmic expression of LCN2 was correlated with lymph node positivity. The nuclear downregulation of LCN2 was correlated with the overexpression of EMT associated proteins (N-cadherin and Twist-related protein 2) and basal biomarkers (cytokeratin 5/6 and epidermal growth factor receptor). Unlike the cytoplasmic expression of LCN2, the loss of nuclear expression was a significant predictor of poor outcome. The combinatorial expression tumours with high cytoplasmic and low nuclear expression were associated with the worst prognosis.

CONCLUSIONS: Tumour cell expression of LCN2 plays a role in breast cancer progression with loss of its nuclear expression is associated with aggressive features and poor outcome. Further functional analysis is warranted to confirm the relationship between the subcellular localisation LCN2 and behaviour of breast cancer.

Citation

Kurozumi, S., Alsaeed, S., Orah, N., Miligy, I. M., Joseph, C., Aljohani, A., …Rakha, E. A. (2020). Clinicopathological significance of lipocalin 2 nuclear expression in invasive breast cancer. Breast Cancer Research and Treatment, 179, 557–564. https://doi.org/10.1007/s10549-019-05488-2

• Journal Article Type: Article
• Acceptance Date: Oct 29, 2019
• Online Publication Date: Nov 9, 2019
• Publication Date: Feb 1, 2020
• Deposit Date: Nov 13, 2019
• Publicly Available Date: Nov 10, 2020
• Journal: Breast Cancer Research and Treatment
• Print ISSN: 0167-6806
• Electronic ISSN: 1573-7217
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 179
• Pages: 557–564
• DOI: https://doi.org/10.1007/s10549-019-05488-2
• Keywords: Invasive breast cancer; Lipocalin 2; Epithelial–mesenchymal transition; N-cadherin; Basal type
• Public URL: https://nottingham-repository.worktribe.com/output/3258560
• Publisher URL: https://link.springer.com/article/10.1007%2Fs10549-019-05488-2
• Additional Information: This is a post-peer-review, pre-copyedit version of an article published in Breast Cancer Research and Treatment. The final authenticated version is available online at: http://dx.doi.org/10.1007/s10549-019-05488-2
• Contract Date: Nov 13, 2019