Ki-67 evaluation in breast cancer: The daily diagnostic practice

Context: Breast cancer is the most common malignancy in females. It is routinely classified according to the WHO histological typing. However, there is also a molecular classification of breast cancer which is routinely substituted with surrogate subtypes based on expression of estrogen, progesterone, and human epidermal growth factor receptor 2 receptors and proliferation index (PI). PI is defined as the percentage of Ki-67-positive cells among overall cell population. The method commonly applied by pathologists to determine PI is visual scoring of the sample. Strict recommendations for PI assessment do not exist. Thus, the mode of PI evaluation differs significantly between pathologists. Aims: The aim of our study was to evaluate the daily approach to defining the PI. Settings and Design: Four practicing nonscholar pathologists were asked to evaluate PI in cases of invasive breast carcinoma. Subjects and Methods: The study was performed on a group of 98 patients diagnosed with invasive breast carcinoma. Immunohistochemical reaction was performed with monoclonal antibody against human Ki-67 antigen using Ventana BenchMark XT. Statistical Analysis Used: Results were compared using Pearson's and Spearman's rank correlation coefficients and Fleiss and Cohen's kappa values. Results: Statistical analysis showed pairwise Pearson's coefficients ranging between 0.77 and 0.84 (P < 0.001) and Spearman's rank correlation coefficients ranging between 0.68 and 0.83 (P < 0.001). The Fleiss kappa value for the 14% cutoff point was 0.58 whereas for the 20% cutoff point was 0.60. The pairwise Cohen's kappa values ranged from 0.45 to 0.69 for the 14% cutoff point and 0.53 to 0.67 for the 20% cutoff point. Friedman's rank ANOVA test showed significant differences among the four pathologists (P < 0.001). Conclusions: Our study shows a significant difference in results and methods of evaluation of PI between pathologists.