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Subspecialized breast pathologists have suboptimal interobserver agreement in Ki-67 evaluation using 20% as the cutoff

  • Original Laboratory Investigation
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

Ki-67 expression levels in breast cancer have prognostic and predictive significance. Therefore, accurate Ki-67 evaluation is important for optimal patient care. Although an algorithm developed by the International Ki-67 in Breast Cancer Working Group (IKWG) improves interobserver variability, it is tedious and time-consuming. In this study, we simplify IKWG algorithm and evaluate its interobserver agreement among breast pathologists in Ki-67 evaluation.

Methods

Six subspecialized breast pathologists (4 juniors, 2 seniors) assessed the percentage of positive cells in 5% increments in 57 immunostained Ki-67 slides. The time spent on each slide was recorded. Two rounds of ring study (R1, R2) were performed before and after training with the modified IKWG algorithm (eyeballing method at 400× instead of counting 100 tumor nuclei per area). Concordance was assessed using Kendall’s and Kappa coefficients.

Results

Analysis of ordinal scale ratings for all categories with 5% increments showed almost perfect agreement in R1 (0.821) and substantial in R2 (0.793); Seniors and juniors had substantial agreement in R1 (0.718 vs. 0.649) and R2 (0.756 vs. 0.658). In dichotomous scale analysis using 20% as the cutoff, the overall agreement was moderate in R1 (0.437) and R2 (0.479), among seniors (R1: 0.436; R2: 0.437) and juniors (R1: 0.445; R2: 0.505). Average scoring time per case was higher in R2 (71 vs. 37 s).

Conclusion

The modified IKWG algorithm does not significantly improve interobserver agreement. A better algorithm or assistance from digital image analysis is needed to improve interobserver variability in Ki-67 evaluation.

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Author notes

  1. Di Ai and Gulisa Turashvili have contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Emory University, 1364 Clifton Rd NE, Atlanta, GA, 30322, USA

    Di Ai, Gulisa Turashvili, Sandra Gjorgova Gjeorgjievski, Qun Wang, Abdulwahab M. Ewaz, Yuan Gao, Thi Nguyen & Xiaoxian Li

  2. General Dynamics Information Technology Inc., Falls Church, VA, USA

    Chao Zhang

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  1. Di Ai
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  2. Gulisa Turashvili
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Correspondence to Xiaoxian Li.

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One author (DA) has worked as a consultant to PathAI. Other authors declare that they have no conflict of interest.

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Ai, D., Turashvili, G., Gjeorgjievski, S.G. et al. Subspecialized breast pathologists have suboptimal interobserver agreement in Ki-67 evaluation using 20% as the cutoff. Breast Cancer Res Treat 204, 415–422 (2024). https://doi.org/10.1007/s10549-023-07197-3

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