The Satisfactory Reproducibility of the Ki-67 Index in Breast Carcinoma, and Its Poor Correlation with the Recurrence Score
Varsha Manucha, Xinmin Zhang, Rebecca M Thomas. Temple University Hospital, Philadelphia, PA
Background: Immunohistochemical assessment of Ki-67 proliferative index (PI) has been established as a valuable prognostic marker in early breast cancer; however, its role in predicting response to neoadjuvant chemotherapy is still uncertain. Lack of an accepted validated method of assessment of Ki-67 and wide variations in the cutoffs has severely limited its clinical utility. In this study, we attempt to assess the intralaboratory interobserver variability in estimation of Ki-67 PI using the guidelines for analysis proposed by the International Breast Cancer Working Group (IBCWG). We further assessed the relationship between the Ki-67 PI and the Recurrence Score (RS) obtained from Oncotype Dx to evaluate its value in predicting tumor recurrence/response to neoadjuvant therapy.
Design: 27 invasive breast carcinomas that were analyzed with the Oncotype Dx assay over a 4 year period were included in the study. H+E sections and Ki-67 (MIB-1 clone, prediluted,Ventana) immunostaining was independently reviewed by three pathologists (RT, XZ, VM). Ki -67 PI was calculated in a minimum of three randomly selected high power fields (40X) including hot spots if present or a minimum of 500 cells, based on the recommendation of the IBCWG. The inter-rater agreement was calculated using intraclass correlation coefficient (ICC). Pearson corelation was used to compare the mean Ki-67 PI with the recurrence score (Oncotype Dx).The RS classifies tumors into 3 risk categories: low (0-17), intermediate (18-30) and high (31-100).
Results: In the 27 tumors, the Ki-67 PI assessment by the three pathologists had significant differences in some cases yet the raters were 89.1% in overall agreement (ICC = 0.891, 95% confidence interval 0.806 - 0.945). There was no correlation between Ki-67 and Oncotype Dx (r=0.081, p=0.694). Of the 26 cases (one case did not have adequate material), there were 10 with low risk (mean group RS: 10.1; mean Ki-67: 17.4; Ki-67 range: 3-33%); 14 with intermediate risk (mean group RS: 21.4; mean Ki-67: 19.5; Ki-67 range: 6-43%) and 3 with high risk (mean group RS: 53; mean Ki-67: 70; Ki-67 range: 55-91%).
Conclusions: Microscopic evaluation of Ki-67 index is reproducible using the method suggested by the IBCWG. The extremely wide range of Ki-67 PI in low and intermediate risk groups, the unexpected low Ki-67 in intermediate risk groups, and the unexpected high Ki-67 PI in low risk groups, limits its use as a predictive measure in these categories. The significance of Ki-67 in the high risk group needs further evaluation in larger scale study.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 55, Tuesday Afternoon