MITOSIN (A NEW PROLIFERATION MARKER) CORRELATES WITH CLINICAL OUTCOMEIN NODE-NEGATIVE BREAST-CANCER

Tumor proliferation rate is an important prognostic factor in breast c ancer, and S-phase fraction (SPF), as measured by flow cytometry, is t he most clinically validated of several methods for measuring it. Howe ver, flow cytometry is not web suited to evaluating the formalin-fixed , paraffin-embedded tumors that are routinely available or to the incr easing number of small breast cancers. These and other limitations hav e motivated research into alternative methods for measuring proliferat ion, including immunohistochemistry (THC) against cell cycle-related a ntigens, which are better suited for the evaluation of small archival tissue samples. Mitosin is a recently described 350 kD nuclear phospho protein that is expressed in the late G(1), S, G(2), and M phases of t he cell cycle but not in G(0). Using a new monoclonal antibody (14C10) , this pilot study evaluated mitosin expression by IHC in a series of 386 node-negative, formalin-fixed, archival breast cancers and correla ted the results with several prognostic factors and clinical outcome ( median follow-up, 78 months; range 3-214 months). The median and range of mitosin positive cells were 7% and 1-47%, respectively. There was a strong positive correlation between mitosin and SPF (r = 0.57; P = 0 .0001), and there were significant negative correlations with estrogen receptor, progesterone receptor, and patient age. Mitosin was not rel ated to overall survival in this pilot study. However, in a univariate cutpoint analysis of disease-free survival (DFS), patients with high levels of mitosin (>9% positive cells) had significantly worse DFS tha n did patients with lower levels (68% versus 84% at 5 years, respectiv ely). In a multivariate analysis of DFS, large tumor size (>2 cm) and high mitosin were the only independently significant predictors of rec urrence (relative risks = 2.47 and 1.72, respectively) in a model cont aining the additional factors estrogen receptor, progesterone receptor , patient age, and SPF. These preliminary results suggest that mitosin as assessed by IHC may be superior to SPF as a prognostic factor in n ode-negative breast cancer, but additional studies are necessary to va lidate these promising findings.