Correlation of Ki-67 antigen expression with mitotic figure index and tumor grade in breast carcinomas using the novel “paraffin”-reactive MIB1 antibody

Abstract

Tumor proliferation is inversely associated with survival in patients with breast carcinoma. Although the proliferation marker Ki-67 antigen correlates with mitotic figure count (MFC) in breast carcinoma (number of mitotic figures per high-powered field), the more precise association of Ki-67 antigen expression with mitotic figure index (MFI) (number of mitotic figures per tumor cells) and histologic grade remains incompletely defined, especially when using the new “paraffin”-reactive monoclonal antibody MIB1 to mark the Ki-67 antigen. To determine the association of Ki-67 antigen expression with mitotic figure content we immunostained 50 formalin-fixed, paraffin-embedded breast carcinomas with the MIB1 monoclonal antibody and correlated the results with MFC, MFI, and Scarff-Bloom-Richardson grade. The Ki-67 antigen-labeling index (K 67LI) was the number of MIB1-positive cells/1,000 tumor cells, the MFI was the number of mitotic figures/1,000 tumor cells, and the MFC was the number of mitotic figures/10 high-powered fields. The K 67LI correlated highly with the MFI ( r = .76, P < .0001), MFC ( r = .78, P < .0001), and Scarff-Bloom-Richardson grade ( r = .73, P < .0001). In addition, analysis of variance showed that MFI was more precise than MFC in estimating K 67LI and thus a more repeatable measure of tumor proliferation. Moreover, measurements made by MFI were as precise as those made by K 67LI. Therefore, the correlation of K 67LI with mitotic figure content was strong enough to suggest that a very carefully measured MFI provides an estimate of tumor growth fraction equivalent to the K 67LI. However, which method is optimal for estimating tumor proliferation rate remains unclear.