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Combined proliferation and apoptosis index provides better risk stratification in breast cancer

Ibrahim, Asmaa; Toss, Michael S.; Atallah, Nehal M.; Al Saleem, Mansour; Green, Andrew R.; Rakha, Emad A.

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Authors

Asmaa Ibrahim

Nehal M. Atallah

Mansour Al Saleem

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



Abstract

Aims: Breast cancer (BC) risk stratification is critical for predicting behaviour and guiding management decision-making. Despite the well-established prognostic value of cellular proliferation in BC, the interplay between proliferation and apoptosis remains to be defined. In this study, we hypothesised that the combined proliferation and apoptosis indices can provide a more accurate in-vivo growth rate measure and a precise prognostic predictor. Methods and results: Apoptotic and mitotic figures were counted in whole slide images (WSI) generated from haematoxylin and eosin-stained sections of 1545 BC cases derived from two well-defined BC cohorts. Counts were carried out visually within defined areas. There was a significant correlation between mitosis and apoptosis scores. High apoptotic counts were associated with features of aggressive behaviour, including high grade, high pleomorphism score and hormonal receptor negativity. Although the mitotic index (MI) and apoptotic index (AI) were independent prognostic indicators, the prognostic value was synergistically higher when combined. BCpatients with a high combined AI and MI had theshortest survival. Replacing the mitosis score with the mitosis–apoptosis index in the Nottingham grading system revealed that the modified grade with the new score had a higher significant association with BC-specific survival with a higher hazard ratio. Conclusion: Apoptotic figures count provides additional prognostic value in BC when combined with MI; such a combination can be implemented to assess the behaviour of BC and provides an accurate prognostic indicator. This can be considered when using artificial intelligence algorithms to assess proliferation in BC.

Citation

Ibrahim, A., Toss, M. S., Atallah, N. M., Al Saleem, M., Green, A. R., & Rakha, E. A. (2023). Combined proliferation and apoptosis index provides better risk stratification in breast cancer. Histopathology, 82(7), 1029-1047. https://doi.org/10.1111/his.14887

Journal Article Type Article
Acceptance Date Feb 9, 2023
Online Publication Date Mar 6, 2023
Publication Date 2023-06
Deposit Date Feb 20, 2023
Publicly Available Date Mar 7, 2024
Journal Histopathology
Print ISSN 0309-0167
Electronic ISSN 1365-2559
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 82
Issue 7
Pages 1029-1047
DOI https://doi.org/10.1111/his.14887
Keywords Breast cancer; Apoptosis; count; methods
Public URL https://nottingham-repository.worktribe.com/output/17645694
Publisher URL https://onlinelibrary.wiley.com/doi/abs/10.1111/his.14887
Additional Information This is the peer reviewed version of the following article: Ibrahim, A., Toss, M.S., Atallah, N.M., Al Saleem, M., Green, A.R. and Rakha, E.A. (2023), Combined proliferation and apoptosis index provides better risk stratification in breast cancer. Histopathology, which has been published in final form at https://doi.org/10.1111/his.14887 The article must be linked to Wiley’s version of record on Wiley Online Library

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