Multi-institutional evaluation of guidance from International Ki67 Working Group vs National Health Commission of China on Immunohistochemistry-based Ki67 assessment

Purpose: Recommendations from N ational H ealth C ommission of C hina (NHCC) and I nternational K i67 W orking G roup (IKWG) were issued respectively to guide immunohistochemistry (IHC)-based Ki67 scoring for breast cancer patients in daily clinical practice. They were evaluated in this multi-institutional study alongside with results from Quantitative Dot Blot (QDB) method. Method: Three sections each from 40 primary ER+ breast cancer resection blocks were randomly assigned a number from 1 to 120 for Ki67 staining and reviewed by 21 pathologists while the other three alternative sections were sent for QDB analysis of Ki67 protein levels. Ki67 scores were grouped by 5/30% (IKWG), 10/30% (NHCC) and 20/30% (NHCC appendix 9, NHCCa9) respectively while QDB results were grouped by C 5 -C 95 of 2.31 nmole/g defined in previous study as low, intermediate and high risk groups. Results: The overall Intraclass Correlation Coefficient (ICC) was 0.785 for IHC evaluations from 21 pathologists, with the Fleiss Kappa at 0.555, 0.628 and 0.480 when Ki67 scores were grouped by the guidance from IKWG, NHCC and NHCCa9 respectively. In comparison, the ICC and Fleiss kappa for QDB analysis were at 0.939 and 0.831. When IHC and QDB results were cross-referenced, more specimens were grouped as high risk by QDB than IHC, and NHCCa9 led to highest percentage of disagreement between two methods. Conclusion: The IKWG recommendation was harder to achieve categorized agreement among pathologists than that of NHCC, yet it led to best agreement with QDB to define low-risk group. QDB method offered significantly improved consistency over current IHC-based Ki67 assessment.