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 = 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] = 1.48; 95% confidence interval [CI] = 1.119‐1.966; P = .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 = 1.19; 95% CI = 1.03‐1.37; P = .01). The ratio of MAP‐tau to stathmin expression showed a positive correlation to disease‐free survival (HR = 0.679; 95% CI = 0.517‐0.891; P = .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 = .0009). Cox multivariate analysis showed the ratio of MAP‐tau to stathmin was an independent predictor of overall survival (HR = 0.609; 95% CI = 0.422‐0.879; P = .008). CONCLUSIONS: Low stathmin and high MAP‐tau are associated with increased microtubule stability and better prognosis in breast cancer. Cancer 2012. © 2012 American Cancer Society.