Comparative prognostic value of Ki-67 and MIB-1 proliferation indices in breast cancer

Tumor proliferation index was evaluated in 246 samples of breast carcinoma using Ki-67 and MIB-1 monoclonal antibodies on frozen and paraffin sections, respectively, with the purpose to compare the two proliferation indices from both a quantitative and prognostic point of view.

All determinations were performed with the same immunohistochemical procedure (Avidin-Biotin Complexes). The prognostic relevance of tumor proliferation index, defined by both the antibodies, was investigated in 127 patients. Ki-67 and MIB-1 median values were used to obtain two groups of patients at different risk and life-table analysis (Mantel-Cox) was performed to assess the probabilities of overall survival (OS) and relapse-free survival (RFS). The median time of observation was 61 months.

Ki-67 and MIB-1 values were exponentially distributed with overlapping ranges varying from 2% to 90%. Ki-67 mean and median values were 16.7% and 14.0%, respectively, compared to 22.5% and 20% for MIB-1. Ki-67 and MIB-1 mean values were statistically different (t = -4.396; p < 0.001), while no difference was observed for MIB-1 mean values on frozen and paraffin sections (t = 1.35; p = n.s.). Ki-67 and MIB-1 values were statistically correlated (Spearman's coefficient = 0.75; p < 0.0001) and directly associated (agreement rate = 79.3%; p < 0.0001). Patients with tumors having a high proportion of MIB-1 positive cells showed a higher 5-year probability of relapse of disease (43.7% versus 27.6%; p = 0.02) and death (35.4% versus 15.8%; p = 0.007) than those with a low one. In parallels Ki-67 was found to be prognostically relevant for OS (32.2% versus 16.2%; p = 0.02) but not for RFS (40.7% versus 27.9%; p = 0.10).

Such results indicate that the detection of proliferative activity on paraffin sections with MIB-1 monoclonal antibody provides in formation analogous to or even better than that obtained with Ki-67 antibody on frozen ones. Moreover, it represents a valuable tool to obtain kinetic data on "routine" histological samples and, above all, to give prognostic evaluations on the clinical outcome of breast cancer patients.