Stathmin expression and its relationship to microtubule-associated protein tau and outcome in breast cancer

BACKGROUND: Microtubule-associated proteins (MAPs) endogenously regulate microtubule stability. Here, the prognostic value of stathmin, a destabilizing protein, was assessed in combination with MAP-tau, a stabilizing protein, in order to evaluate microtubule stabilization as a potential biomarker. METHODS: Stathmin and MAP-tau expression levels were measured in a breast cancer cohort (n ¼ 651) using the tissue microarray format and quantitative immunofluorescence (AQUA) technology, then correlated with clinical and pathological characteristics and disease-free survival. RESULTS: Univariate Cox proportional hazard models indicated that high stathmin expression predicts worse overall survival (hazard ratio [HR] ¼ 1.48; 95% confidence interval [CI] ¼ 1.119-1.966; P ¼ .0061). Survival analysis showed 10-year survival of 53.1% for patients with high stathmin expression versus 67% for low expressers (log-rank, P < .003). Cox multivariate analysis showed high stathmin expression was independent of age, menopausal status, nodal status, nuclear grade, tumor size, and estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression (HR ¼ 1.19; 95% CI ¼ 1.03-1.37; P ¼ .01). The ratio of MAP-tau to stathmin expression showed a positive correlation to disease-free survival (HR ¼ 0.679; 95% CI ¼ 0.517-0.891; P ¼ .0053) with a 10-year survival of 65.4% for patients who had a high ratio of MAP-tau to stathmin versus 52.5% 10-year survival rate for those with a low ratio (log-rank, P ¼ .0009). Cox multivariate analysis showed the ratio of MAP-tau to stathmin was an independent predictor of overall survival (HR ¼ 0.609; 95% CI ¼ 0.422-0.879; P ¼ .008). CONCLUSIONS: Low stathmin and high MAP-tau are associated with increased microtubule stability and better prognosis in breast cancer. Cancer 2012;118:4660-9. V C 2012 American Cancer Society.