Ki-67 Quantification in Breast Cancer: A Comparison of Hotspot and Global Scoring Methods Using a Standardized...

Area of Science:

• Oncology
• Pathology
• Biomarker Analysis

Background:

• Ki-67 immunohistochemistry is a crucial proliferative biomarker in breast carcinoma, but variability in assessment methods hinders reproducibility and clinical utility.
• The International Ki-67 in Breast Cancer Working Group (IKWG) developed a standardized global scoring method and an Android application to address these limitations.

Purpose of the Study:

• To compare hotspot and weighted-global Ki-67 scoring methods using the IKWG Android application in invasive breast carcinoma.
• To assess the correlation and categorization between scoring methods and evaluate their diagnostic performance for predicting histological grade.

Main Methods:

• A cross-sectional study of 53 invasive breast carcinoma cases.
• Digital scanning of Ki-67 immunohistochemical slides.
• Scoring using both hotspot and weighted-global methods via the IKWG Android application, followed by statistical analysis (Mann-Whitney U, Spearman's correlation, ROC).

Main Results:

• The weighted-global method yielded a lower mean Ki-67 index (43.1%) compared to the hotspot method (57.1%; p=0.004).
• Both methods showed a strong correlation (Spearman's r = 0.954, p < 0.001).
• The weighted-global Ki-67 demonstrated excellent diagnostic performance for high-grade tumors (AUC = 0.991), with 100% specificity and 84.9% accuracy.

Conclusions:

• Hotspot scoring systematically overestimates tumor proliferation in breast carcinoma.
• The weighted-global method, accounting for intratumoral heterogeneity, provides a more biologically representative Ki-67 assessment.
• Standardization with the IKWG Android application enhances reproducibility and supports reliable clinical decision-making for breast cancer treatment stratification.