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

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 MIBI 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 (K67LI) was the number of MIBI-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 K67LI 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 K67LI and thus a more repeatable measure of tumor proliferation. Moreover, measurements made by MFI were as precise as those made by K67LI. Therefore, the correlation of K67LI 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 K67LI. However, which method is optimal for estimating tumor proliferation rate remains unclear.