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

Abstract

Summary MIBl proliferation rate (MIBl-PR) and total S-phase fraction (SPF) were retrospectively determined in formalin-fixed, paraffinembedded 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 (1 6-72 months). lmmuno6taining of Ki-67 antigen was performed using the monoclonal antibody MIBl and the APAAP technique. An adjacent 50-gm paraffin section was used for flow cytometric S-phase determination. Results were compared to established clinicopathological prognostic factors. MIBl -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 MIBl -PR and SPF was found in aneuploid (P = 0.025) but not in diploid tumours (P = 0.164). In univariate analysis, both MIBl -PR (optimized cut-off of 25%) and SPF (optimized cut-off of 8%) were significant prognostic factors for disease-free survival (DFS) (MIBl -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 MIBl -PR or established clinicopathological prognostic factors. We thus conclude that MIBl-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.

Efeitos de diferentes doses de tamoxifeno sobre a proliferação celular do epitélio mamário

“…A imunorreatividade do Ki-67 foi avaliada quantitativamente, contando-se, no mínimo, 500 células 17,21 . Da relação entre as células com nú-cleos corados e não corados, multiplicada por 100, obteve-se o percentual de positividade para cada caso.…”

Optimizing flow cytometric DNA ploidy and S‐phase fraction as independent prognostic markers for node‐negative breast cancer specimens

“…Other investigators used Total S-phase as a means of pooling the diploid and aneuploid S-phases into a single prognostic model (64,65). The problem with this ap- *% DCV, diploid G1 % CV; Total, total modeled events; % Bad, % background aggregates and debris; RCS, reduced chi-square.…”

High cyclin B1 expression is associated with poor survival in breast cancer

“…A new entity, the so-called triple negative (oestrogen receptor, progesterone receptor and HER2 negative) breast cancer has a highly aggressive clinical course with shorter recurrence-free and overall survival (Dent et al, 2007). High proliferation rate has also been shown to associate with poor breast cancer survival (Dettmar et al, 1997;Bryant et al, 1998;Ahlin et al, 2007). Newer methods utilising complementary DNA (cDNA) have been developed aiming at more specific prognostic evaluation than by immunohistochemical methods van't Veer et al, 2002;Paik et al, 2004).…”