PROGNOSTIC IMPACT OF PROLIFERATION-ASSOCIATED FACTORS MIBI (KI-67) AND S-PHASE IN NODE-NEGATIVE BREAST-CANCER

MIB1 proliferation rate (MIB1-PR) and total S-phase fraction (SPF) wer e retrospectively determined in formalin-fixed, paraffin-embedded sect ions of 90 primary node-negative breast carcinomas. None of the patien ts had received adjuvant systemic therapy. Median follow-up in patient s still alive at the time of analysis was 37.5 months (16-72 months). Immunostaining of Ki-67 antigen was pet-formed using the monoclonal an tibody MIB1 and the APAAP technique. An adjacent 50-mu m paraffin sect ion was used for flow cytometric S-phase determination. Results were c ompared to established clinicopathological prognostic factors. MIBI-PR was significantly correlated to grading (P = 0.018); SPF was signific antly correlated with tumour size (P = 0.041) and inversely with stero id hormone receptor status (P = 0.03). A significant correlation betwe en MIBI-PR and SPF was found in aneuploid (P = 0.025) but not in diplo id tumours (P = 0.164). In univariate analysis, both MIB1-PR (optimize d cut-off of 25%) and SPF (optimized cut-off of 8%) were significant p rognostic factors for disease-free survival (DFS) (MIB1-PR, P = 0.0224 ; SPF, P = 0.0028). in multivariate analysis, however, only SPF remain ed significant; it was the strongest prognostic factor for DFS (P = 0. 0073), stronger than MIB1-PR or established clinicopathological progno stic factors. We thus conclude that MIBI-PR and SPF provide additional prognostic information in node-negative breast cancer. However, in ou r study, flow cytometrically determined SPF had the greater prognostic impact.