Volume 80, February 2026, 152571Author links open overlay panel, , Highlights•

Excellent interobserver reproducibility of Ki-67 in CNB and resection.

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CNB showed slightly higher Ki-67 than matched resections on average.

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Clinically relevant CNB–resection discordance persisted near cut-offs.

Abstract

Ki-67 is a nuclear protein linked to cellular proliferation and is used as a prognostic and predictive biomarker in breast carcinoma. However, variability in its assessment limits its clinical utility. This study evaluated interobserver reproducibility in Ki-67 scoring and compared proliferative indices between core needle biopsy (CNB) and corresponding resection specimens in invasive breast carcinoma. Sixty-three cases with matched CNB and resection specimens were retrospectively analyzed. Ki-67 immunohistochemistry was independently evaluated by two pathologists using manual image-based counting. Interobserver agreement and CNB–resection concordance were assessed using the intraclass correlation coefficient (ICC), Cohen's kappa, Bland–Altman analysis, and Spearman's correlation. Tumor characteristics were analyzed for their association with variability. Interobserver agreement was excellent, with ICCs of 0.89 for CNB and 0.91 for resection specimens. Cohen's kappa for binary classification (<20 % vs. ≥20 %) showed moderate agreement for CNB (κ = 0.54) and substantial agreement for resections (κ = 0.78). Bland–Altman analysis revealed small but consistent bias, with CNB values slightly higher (+2.89 % and + 2.25 % for raters 1 and 2, respectively). However, discrepancies >10 % were observed in some cases. Tumor characteristics had minimal to no association with scoring variability. Despite excellent statistical agreement, clinically significant variability in Ki-67 scoring may occur. These findings support interpreting Ki-67 as a continuous variable rather than relying on fixed cutoffs. Pathologists should consider specimen type and scoring limitations when reporting Ki-67, and may recommend which value is more reliable or suggest retesting when appropriate.

Keywords

Breast carcinoma

Proliferative index

Ki-67

Core needle biopsy

Resection

Reproducibility

Data availabilityThe data supporting the findings of this study are openly available in Mendeley Data at DOI: 10.17632/97fvt6c7wb.1.[17]..

© 2025 The Authors. Published by Elsevier Inc.