Prognostic relevance of proliferative activity evaluated by Mib-1 immunostaining in node negative breast cancer

Abstract 

Aim

The purpose of this prospective observational study was to analyze the role of Mib-1 immunostaining as a proliferation index in breast cancer. Correlations between Mib-1 expression and clinico-pathological characteristics as well as its prognostic value have been studied in a series of 432 node negative breast cancers.

Methods

Mib-1 expression was evaluated by immunohistochemistry. Tumor sections from highly cellular invasive areas of cancer were stained by monoclonal antibody Mib-1 (Dako) and cells whose nuclei stained positive were counted in 10 randomly chosen HPFs and expressed as percentages of all epithelial cells. A minimum of 400 cells were counted. Correlation between Mib-1 staining and clinico-pathological factors was investigated by means of univariate and multivariate analyses. The prognostic impact on actuarial disease free (DFS) and overall survival (OS) was evaluated by univariate analysis using the log-rank test and by multivariate analysis using Cox regression model.

Results

Tumors were considered as positive for Mib-1 expression when more than 15% of cells counted were stained. Mib-1 positivity was found in 190/432 cases and resulted in being significantly related to tumor grade, tumor size and absence of estrogen receptors at multivariate analysis.

With a median follow-up of 66 months, Mib-1 positivity resulted in being the only independent predictor of OS (RR 2.92), and an independent predictor of DFS (RR 2.01) together with absence of estrogen receptors (RR 2.15).

Conclusions

Mib-1 index of proliferative activity correlates well to other established prognostic factors of breast cancer. Mib-1 index may improve the tailoring of adjuvant therapy in early breast cancer, and our experience adds evidence to its effectiveness as prognostic factor. Efforts to reach uniformity in the methodology and in the scoring system should be done to warrant a standardized procedure and make Mib-1 determination definitively reliable in the current clinical practice.

Keywords: Breast cancer, Prognosis, Proliferation index, Mib-1, Multivariate analysis, Prospective study