Quantitative image analysis of MIB-1 immunoreactivity. A comparison with flow cytometric assessment of proliferative activity in invasive carcinoma of the breast

Abstract

Proliferative activity, especially flow cytometrically determined S-phase fraction, is generally accepted as an important prognostic indicator in carcinoma of the breast. We studied cellular proliferation in 53 breast carcinomas using quantitative image analysis of immunoreactivity to a recently available monoclonal antibody, MIB-1, which is applicable to formalin-fixed, paraffin-embedded tissues. MIB-1 is a murine monoclonal antibody that reacts with the Ki-67 nuclear antigen expressed by proliferating cells in the late G1, and G2/M phases of the cell cycle. These results were compared to flow cytometric determinations of S-phase and S + G2/M phase fractions obtained from corresponding fresh tissue samples. There was a good correlation between quantitative immunoreactivity to MIB-1 as measured by image analysis and flow cytometric S-phase and S + G2/M phase fractions (r = .63, P < .00001; r = .607, P < .00001, respectively). Immunoreactivity to MIB-1 and flow cytometric S-phase and S + G2/M phase fractions were significantly increased in aneuploid tumors as compared to diploid tumors. Histologic grade correlated with flow cytometric S-phase and S + G2/M phase fractions and MIB-1 immunoreactivity as determined by image analysis. There was a correlation between tumor size and MIB immunoreactivity. No proliferative parameters significantly correlated with lymph node status. Assessment of proliferative activity by quantitative image analysis of immunoreactivity to monoclonal MIB-1 antibody may be employed in cases of invasive carcinoma of the breast in which flow cytometric analysis fails to result in quantitative proliferative values, or it may be used as an alternative measurement of such proliferative activity.