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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 3/2020

01-02-2020 | Metastasis | Preclinical study

Clinicopathological significance of lipocalin 2 nuclear expression in invasive breast cancer

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

Published in: Breast Cancer Research and Treatment | Issue 3/2020

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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 = 1363). 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 which 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.
Appendix
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Metadata
Title
Clinicopathological significance of lipocalin 2 nuclear expression in invasive breast cancer
Authors
Sasagu Kurozumi
Sami Alsaeed
Nnamdi Orah
Islam M. Miligy
Chitra Joseph
Abrar Aljohani
Michael S. Toss
Takaaki Fujii
Ken Shirabe
Andrew R. Green
Mohammed A. Aleskandarany
Emad A. Rakha
Publication date
01-02-2020
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2020
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-019-05488-2

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