부산대학교 도서관

Purpose: Quantification of Ki67 in breast cancer is a well-established prognosticand predictive marker, but inter-laboratory variability has hampered its clinicalusefulness. This study compares the prognostic value and reproducibility of Ki67scoring using four automated, digital image analysis (DIA) methods and two manualmethods.Methods: The study cohort consisted of 367 patients diagnosed between 1990 and2004, with hormone receptor positive, HER2 negative, lymph node negative breastcancer. Manual scoring of Ki67 was performed using predefined criteria. DIA Ki67scoring was performed using QuPath and Visiopharm® platforms. Reproducibility wasassessed by the intraclass correlation coefficient (ICC). ROC curve survival analysisidentified optimal cutoff values in addition to recommendations by the InternationalKi67 Working Group and Norwegian Guidelines. Kaplan–Meier curves, log-rank test andCox regression analysis assessed the association between Ki67 scoring and distantmetastasis (DM) free survival.Results: The manual hotspot and global scoring methods showed good agreement whencompared to their counterpart DIA methods (ICC > 0.780), and good to excellentagreement between different DIA hotspot scoring platforms (ICC 0.781–0.906).Different Ki67 cutoffs demonstrate significant DM-free survival (p < 0.05). DIAscoring had greater prognostic value for DM-free survival using a 14% cutoff (HR3.054–4.077) than manual scoring (HR 2.012–2.056). The use of a single cutoff for allscoring methods affected the distribution of prediction outcomes (e.g. falsepositives and negatives).Conclusion: This study demonstrates that DIA scoring of Ki67 is superior to manualmethods, but further study is required to standardize automated, DIA scoring anddefinition of a clinical cut-off.