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

Abstract

Introduction
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. BC patients with a high combined AI and MI had the shortest 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. (2023). Combined proliferation and apoptosis index provides better risk stratification in breast cancer. Histopathology, https://doi.org/10.1111/his.14887

• Journal Article Type: Article
• Acceptance Date: Feb 9, 2023
• Online Publication Date: Feb 13, 2023
• Publication Date: Feb 13, 2023
• Deposit Date: Feb 20, 2023
• Publicly Available Date: Feb 14, 2024
• Journal: Histopathology
• Print ISSN: 0309-0167
• Electronic ISSN: 1365-2559
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• 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