A Comparison of the Hot Spot and the Average Cancer Cell Counting Methods and the Optimal Cutoff Point of the Ki-67 Index for Luminal Type Breast Cancer

Abstract

Objective: In this case-control study, we investigated the most suitable cell counting area and the optimal cutoff point of the Ki-67 index. Methods: Thirty recurrent cases were selected among hormone receptor (HR)-positive/HER2-negative breast cancer patients. As controls, 90 nonrecurrent cases were randomly selected by allotting 3 controls to each recurrent case based on the following criteria: age, nodal status, tumor size, and adjuvant endocrine therapy alone. Both the hot spot and the average area of the tumor were evaluated on a Ki-67 immunostaining slide. Results: The median Ki-67 index value at the hot spot and average area were 25.0 and 14.5%, respectively. Irrespective of the area counted, the Ki-67 index value was significantly higher in all of the recurrent cases (p < 0.0001). The multivariate analysis revealed that the Ki-67 index value of 20% at the hot spot was the most suitable cutoff point for predicting recurrence. Moreover, higher ΔKi-67 index value (the difference between the hot spot and the average area, ≥10%) and lower progesterone receptor expression (<20%) were significantly correlated with recurrence. Conclusion: A higher Ki-67 index value at the hot spot strongly correlated with recurrence, and the optimal cutoff point was found to be 20%.