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Legumain is an independent predictor for invasive recurrence in breast ductal carcinoma in situ

Toss, Michael S.; Miligy, Islam M.; Gorringe, Kylie L.; McCaffrey, L.; Alkawaz, Abdulbaqi; Abidi, Asima; Ellis, Ian O.; Green, Andrew R.; Rakha, Emad A.

Legumain is an independent predictor for invasive recurrence in breast ductal carcinoma in situ Thumbnail


Authors

Michael S. Toss

Islam M. Miligy

Kylie L. Gorringe

L. McCaffrey

Abdulbaqi Alkawaz

Asima Abidi

EMAD RAKHA Emad.Rakha@nottingham.ac.uk
Professor of Breast Cancer Pathology



Abstract

© 2018, United States & Canadian Academy of Pathology. Legumain is a proteolytic enzyme that plays a role in the regulation of cell proliferation in invasive breast cancer. Studies evaluating its role in ductal carcinoma in situ (DCIS) are lacking. Here, we aimed to characterize legumain protein expression in DCIS and evaluate its prognostic significance. Legumain was assessed immunohistochemically in a tissue microarray of a well-characterized cohort of DCIS (n = 776 pure DCIS and n = 239 DCIS associated with invasive breast cancer (DCIS-mixed)). Legumain immunoreactivity was scored in tumor cells and surrounding stroma and related to clinicopathological parameters and patient outcome. High legumain expression was observed in 23% of pure DCIS and was associated with features of high-risk DCIS including higher nuclear grade, comedo necrosis, hormone receptor negativity, HER2 positivity, and higher proliferation index. Legumain expression was higher in DCIS associated with invasive breast cancer than in pure DCIS (p < 0.0001). In the DCIS-mixed cohort, the invasive component showed higher legumain expression than the DCIS component (p < 0.0001). Legumain was an independent predictor of shorter local recurrencefree interval for all recurrences (p = 0.0003) and for invasive recurrences (p = 0.002). When incorporated with other risk factors, legumain provided better patient risk stratification. High legumain expression is associated with poor prognosis in DCIS and could be a potential marker to predict DCIS progression to invasive disease.

Citation

Toss, M. S., Miligy, I. M., Gorringe, K. L., McCaffrey, L., Alkawaz, A., Abidi, A., …Rakha, E. A. (2019). Legumain is an independent predictor for invasive recurrence in breast ductal carcinoma in situ. Modern Pathology, 32, 639-649. https://doi.org/10.1038/s41379-018-0180-x

Journal Article Type Article
Acceptance Date Nov 1, 2018
Online Publication Date Nov 14, 2018
Publication Date May 1, 2019
Deposit Date Nov 2, 2018
Publicly Available Date May 15, 2019
Journal Modern Pathology
Print ISSN 0893-3952
Electronic ISSN 1530-0285
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 32
Pages 639-649
DOI https://doi.org/10.1038/s41379-018-0180-x
Keywords DCIS; Legumain; Poor prognosis; Invasive recurrence
Public URL https://nottingham-repository.worktribe.com/output/1220181
Publisher URL https://www.nature.com/articles/s41379-018-0180-x

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