MIB-1 proliferation index is an independent predictor oflymph-node metastasis in operable breast carcinoma: aprospective study on 675 patients

Background: MIB-1 index is related to proliferative activity of breastcarcinomas and provides valuable prognostic informations for overall and disease free survival, but few data exist regarding its value as a predictor of axillary metastases. The aim of the present study was to evaluate the role of MIB-1 index, together with other clinicalpathological parameters, as risk factor for lymph-node metastases in patients submitted to axillary dissection. Methods: Six hundred seventy-five consecutive patients operated on between January 1995 and December 2001 were considered. Mean age of patients was 62 ^ 12 (rage 27–94); a mean number of 17 ^ 7 axillary lymphnodes (range 6–50) were removed. In all cases MIB-1 proliferation index was evaluated; a cut-off value of 10% was considered. Expression of p53 and c-erb-B2 were evaluated respectively in 514 and 588 patients. Correlations between MIB-1, other clinical-pathological parameters and lymphnode metastases were evaluated by means of univariate and multivariate analysis. Results: Lymphnode involvement was present in 248 cases (36.7%). High values of MIB-1 were found in 318 patients (47.1%); positivity to MIB-1 correlated significantly with invasive ductal tumors ðp , 0:005Þ; c-erb-B2 and p53 overepression ðp , 0:005Þ; tumor size .1 cm ðp , 0:001Þ and absence of estrogen and progesteron receptors ðp , 0:001Þ: By univariate analysis, vascular invasion ðp , 0:0001Þ; MIB-1 proliferation index ðp , 0:0001Þ; tumor multicentricity ðp , 0:0001Þ; tumor grade ðp , 0:05Þ; tumor size ðp , 0:0001Þ; estrogen ðp , 0:01Þ and progesteron ðp , 0:05Þ receptor status were related to an higher incidence of lymphnode axillary metastases; no correlation with age, histological type, number of removed lymphnodes, p53 and c-erb-B2 overexpression was found. Multivariate analysis, performed by means of a logistic regression model, identified vascular invasion (Relative Risk—RR 7.09, p , 0:0001), tumor multicentricity (RR 3.25, p , 0:0001), tumor size (RR 3.13, p , 0:0001) and MIB-1 proliferation index (RR 1.64, p , 0:05) as independent predictors of lymph nodes metastases. Among 132 patients with monocentric tumors sized less than 1 cm without vascular invasion, the percentage of metastases varied from 8.3% for patients with high MIB-1 index to 6% for patients with low MIB-1 values. Considering 208 patients with pT1c monocentric tumors without vascular invasion, the percentage of axillary metastases varied from 22.4% for MIB-1 positive tumors to 14.9% for MIB-1 negative tumors. Conclusions: MIB-1 proliferation index could provide additional informations about the risk of lymphnode metastases and may support clinical decision on axillary treatment in early breast cancer.