Prognostic value of Mib-1 proliferation index in breast cancer. A prospective study on 669 patients

Background: Cell proliferation has an important role as an indicator of biological aggressiveness in breast cancer. Although not considered an obligatory marker, Mib-1 proliferation index is frequently measured in breast cancer patients as a static marker of proliferative activity. The purpose of our study was to prospectively analyze the prognostic value of the Mib-1 proliferation index in a series of 669 consecutive patients operated on for invasive breast cancer at the Surgical Oncology Section of the Department of Human Pathology and Oncology, University of Siena, Italy. Methods: Mib-1 labeling index was evaluated by immmunohistochemistry, its association with conventional clinico-pathological factors was analysed by univariate analysis and logistic regression and its prognostic impact was evaluated by multivariate analysis. Results: Tumors were considered expressing an high Mib-1 index when >20% of cells counted were stained. A high Mib-1 proliferation index was expressed in 330 cases (49.3%), and resulted significantly related to high tumor grade, tumor size, absence of progesteron receptors and p53 expression. With a median follow-up of 65 months, an independent negative prognostic impact on disease free survival (DFS) was observed for presence of LVI, high Mib-1 index, tumor size, absence of estrogen receptors and number of involved axillary lymphnodes. Independent prognostic factors for overall survival (OS) included tumor size (p<0.05), high Mib-1 index (p<0.05), absence of estrogen receptors (p<0.05) and number of metastatic axillary lymphnodes (p<0.001). Conclusions: These data may indicate that expression of high values of Mib-1 labeling index is a marker of breast cancers with high proliferative activity. The independent prognostic value of Mib-1 index either for DFS and OS supports its use as a marker of tumors with high biological aggressiveness. As a consequence, determination of Mib-1 index may be particularly useful in the clinical setting allowing to identify, together with other established prognostic factors, subsets of patients with high risk of relapse.