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Ki67 assessment in invasive luminal breast cancer: a comparative study between different scoring methods

Lashen, Ayat; Toss, Michael S; Green, Andrew R; Mongan, Nigel P; Rakha, Emad


Ayat Lashen

Michael S Toss

Professor of Breast Cancer Pathology


Background: Ki67 reflects the proliferation activity in breast cancer (BC). However, an optimal method for its assessment in clinical settings has yet to be robustly defined. In this study, we compared several methods to score Ki67 to identify a reliable and reproducible method for routine practice.

Methods: Sections from luminal BC cohort (n=1662) were immunohistochemically stained with Ki67 and were assessed for the percentage, pattern, and intensity of expression. Ki67 positivity was evaluated using three methods: (i) quantification of Ki67 positive cells among 1000 invasive tumour cells within hotspot, (ii) average estimation of Ki67 within a defined hotspot, and (iii) average estimation of Ki67 positivity within the whole section. Time required for scoring, inter-observer agreement and association with outcome were determined.

Results: The mean percentage of Ki67 expression per 1000 cells method was 16%, while the mean value of Ki67 scores using the average estimation within hotspot and whole slide were 14% and 12%, respectively. Quantification of Ki67 positive cells within 1000 cells had the highest degree of consistency between observers, and the highest hazard ratio predicting patient outcome when compared to using different common Ki67 cut-offs, which was independent on the other two methods. Granular pattern of Ki67 expression was associated with poorer outcome as compared to the other patterns.

Conclusion: Assessment of Ki67 expression using quantification positive cells among 1000 tumour cells is an optimal method to achieve high reliability and reproducibility. Comment on the predominant Ki67 expression pattern would add prognostic and predictive value in luminal BC.


Lashen, A., Toss, M. S., Green, A. R., Mongan, N. P., & Rakha, E. (2022). Ki67 assessment in invasive luminal breast cancer: a comparative study between different scoring methods. Histopathology, 81(6), 786-798.

Journal Article Type Article
Acceptance Date Aug 21, 2022
Online Publication Date Sep 19, 2022
Publication Date Dec 1, 2022
Deposit Date Oct 27, 2022
Publicly Available Date Nov 1, 2022
Journal Histopathology
Print ISSN 0309-0167
Electronic ISSN 1365-2559
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 81
Issue 6
Pages 786-798
Keywords General Medicine; Histology; Pathology and Forensic Medicine
Public URL
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