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Breast Cancer Research and Treatment

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Open Access 01-08-2020 | Breast Cancer | Epidemiology

Prognostic potential of automated Ki67 evaluation in breast cancer: different hot spot definitions versus true global score

Authors: Stephanie Robertson, Balazs Acs, Michael Lippert, Johan Hartman

Published in: Breast Cancer Research and Treatment | Issue 1/2020

Abstract

Purpose

The proliferation-associated biomarker Ki67 has potential utility in breast cancer, including aiding decisions based on prognosis, but has unacceptable inter- and intralaboratory variability. The aim of this study was to compare the prognostic potential for Ki67 hot spot scoring and global scoring using different digital image analysis (DIA) platforms.

Methods

An ER+/HER2− breast cancer cohort (n = 139) with whole slide images of sequential sections stained for hematoxylin–eosin, pancytokeratin and Ki67, was analyzed using two DIA platforms. For hot spot analysis virtual dual staining was applied, aligning pancytokeratin and Ki67 images and 22 hot spot algorithms with different features were designed. For global Ki67 scoring an automated QuPath algorithm was applied on Ki67-stained whole slide images. Clinicopathological data included overall survival (OS) and recurrence-free survival (RFS) along with PAM50 molecular subtypes.

Results

We show significant variations in Ki67 hot spot scoring depending on number of included tumor cells, hot spot size, shape and location. The higher the number of scored tumor cells, the higher the reproducibility of Ki67 proliferation values. Hot spot scoring had greater prognostic potential for RFS in high versus low Ki67 subgroups (hazard ratio (HR) 6.88, CI 2.07–22.87, p = 0.002), compared to global scoring (HR 3.13, CI 1.41–6.96, p = 0.005). Regarding OS, global scoring (HR 7.46, CI 2.46–22.58, p < 0.001) was slightly better than hot spot scoring (HR 6.93, CI 1.61–29.91, p = 0.009). In adjusted multivariate analysis, only global scoring was an independent prognostic marker for both RFS and OS. In addition, global Ki67-based surrogate subtypes reached higher concordance with PAM50 molecular subtype for luminal A and B tumors (66.3% concordance rate, κ = 0.345), than using hot spot scoring (55.8% concordance rate, κ = 0.250).

Conclusions

We conclude that the automated global Ki67 scoring is feasible and shows clinical validity, which, however, needs to be confirmed in a larger cohort before clinical implementation.

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Title: Prognostic potential of automated Ki67 evaluation in breast cancer: different hot spot definitions versus true global score
Authors: Stephanie Robertson
Balazs Acs
Michael Lippert
Johan Hartman
Publication date: 01-08-2020
Publisher: Springer US
Keywords: Breast Cancer
Breast Cancer
Published in: Breast Cancer Research and Treatment / Issue 1/2020
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-020-05752-w

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