Prognostic impact of proliferation-associated factors MIB1 (Ki-67) and S-phase in node-negative breast cancer.

MIB1 proliferation rate (MIB1-PR) and total S-phase fraction (SPF) were retrospectively determined in formalin-fixed, paraffin-embedded sections of 90 primary node-negative breast carcinomas. None of the patients had received adjuvant systemic therapy. Median follow-up in patients still alive at the time of analysis was 37.5 months (16-72 months). Immunostaining of Ki-67 antigen was performed using the monoclonal antibody MIB1 and the APAAP technique. An adjacent 50-microm paraffin section was used for flow cytometric S-phase determination. Results were compared to established clinicopathological prognostic factors. MIB1-PR was significantly correlated to grading (P = 0.018); SPF was significantly correlated with tumour size (P = 0.041) and inversely with steroid hormone receptor status (P = 0.03). A significant correlation between MIB1-PR and SPF was found in aneuploid (P = 0.025) but not in diploid tumours (P = 0.164). In univariate analysis, both MIB1-PR (optimized cut-off of 25%) and SPF (optimized cut-off of 8%) were significant prognostic factors for disease-free survival (DFS) (MIB1-PR, P = 0.0224; SPF, P = 0.0028). In multivariate analysis, however, only SPF remained significant; it was the strongest prognostic factor for DFS (P = 0.0073), stronger than MIB1-PR or established clinicopathological prognostic factors. We thus conclude that MIB1-PR and SPF provide additional prognostic information in node-negative breast cancer. However, in our study, flow cytometrically determined SPF had the greater prognostic impact.

[Prognostic significance of the S-phase and MIB1 (Ki-67) proliferation parameters in node-negative breast carcinoma]. / Prognostische Bedeutung der Proliferationsparameter S-Phase und MIB1 (Ki-67) beim nodal-negativen Mammakarzinom.

OBJECTIVE: In 90 patients with primary node-negative breast carcinomas we compared the prognostic impact of total S-phase fraction (SPF) and MIB1 proliferation rate (MIB1-PR) after a median follow-up of 34 months (9-72 months). METHODS: SPF was determined flow cytometrically and MIB1 (Ki-67) immunohistochemically in parallel-cut, paraffin-embedded tissue sections. RESULTS: SPF was significantly correlated to tumor size and steroid hormone receptor status, MIB1-PR to grading. In univariate analysis both SPF and MIB1-PR were significant prognostic factors for disease-free survival. In multivariate analysis however, S-phase fraction was the only significant prognostic factor when compared to MIB1-PR, tumor size, steroid hormone receptor status, menopausal status, grading, lymph vessel invasion, and tumor necrosis. CONCLUSIONS: In our study SPF was of higher prognostic strength and may therefore be better suited for clinical application than MIB1-PR in node-negative breast cancer.