Fig 1.
An example of counting area selection in a tumor with heterogeneous Ki-67 expression.
Three representative areas have been selected including a hot spot (area 1). (Original magnification: x 40 (large photo); x 200 (three small photos)).
Fig 2.
The distribution of Ki-67 labeling indices in 493 luminal breast cancers.
The X-axis represents the individual cases, arranged in ascending order based on their Ki-67 labeling index (LI) measured by the average method. The Y-axis represents the individual Ki-67 LIs measured by the hot spot method (the edge of the light gray area) and the average method (dotted line), and the values measured at the “cold spot”, the area with the lowest Ki-67 LI (the edge of the dark gray area). The extent of the light gray colored area represents the difference between the Ki-67 LI measured at the hot spot and the cold spot (Δ Ki-67).
Table 1.
Clinicopathologic characteristics of 493 primary luminal/HER-negative breast cancers.
Fig 3.
Correlation between Δ Ki-67, H/A ratio and Ki-67 labeling index measured by the two methods.
(A, B) ΔKi-67 is moderately correlated with the Ki-67 labeling index (LI) based on the average method, and highly correlated with Ki-67 LI measured by the hot spot method (Pearson correlation coefficient, 0.535 and 0.731 respectively). (C, D) The H/A ratio is not correlated with Ki-67 LI measured by either method (Pearson correlation coefficients, -0.298 and -0.119, respectively).
Table 2.
Optimal Ki-67 cutoff values for predicting tumor recurrence.
Fig 4.
Kaplan-Meier survival curves of Ki-67 LI based on the average method and hot spot method.
High Ki-67 labeling indices of tumors using a cutoff value of 18% in the average method (A) and 22% in the hot spot method (B) are associated with poor disease-free survival (p = 0.002, p = 0.001, respectively).
Fig 5.
Variability of Ki-67 labeling index in repeated counts.
(A) Twenty breast cancers that were initially classified into the low Ki-67 subgroup using the average method (cutoff value: 18%, dotted line) were re-counted by the same method. Only 3 cases were reclassified into the high Ki-67 subgroup in repeated count. (B) Of the 20 cases, 4 cases were initially classified into the low Ki-67 subgroup by the hot spot method (cutoff value: 22%, dot line). One of these was reclassified into the high Ki-67 subgroup, and 8 of the 16 cases originally classified into the high Ki-67 subgroup were reassigned to the low Ki-67 subgroup after a second count using the same method.
Table 3.
Univariate analysis of factors associated with disease-free survival.
Table 4.
Multivariate survival analysis using Cox proportional hazards regression models.