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

• Published in: Cancer 2012-10, Vol.118 (19), p.4660-4669
• Main Authors: Baquero, Maria T., Hanna, Jason A., Neumeister, Veronique, Cheng, Huan, Molinaro, Annette M., Harris, Lyndsay N., Rimm, David L.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Analysis of Variance; Biological and medical sciences; Biomarkers, Tumor - analysis; Blotting, Western; Breast - chemistry; Breast Neoplasms - chemistry; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Cell Line, Tumor; Cohort Studies; Female; Fluorescent Antibody Technique; Gene Expression Regulation, Neoplastic; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Lymphatic Metastasis; Mammary gland diseases; Medical sciences; microtubule‐associated protein; Middle Aged; Neoplasm Grading; Neoplasm Staging; Odds Ratio; predictive; Predictive Value of Tests; Prognosis; prognostic; Proportional Hazards Models; quantitative analysis; Risk Assessment; Risk Factors; RNA, Small Interfering - metabolism; stathmin; Stathmin - analysis; tau; tau Proteins - analysis; taxanes; Tissue Array Analysis; Treatment Outcome; Tumors
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.27453

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. Modulation of microtubule stabilization is associated with outcome. Increased expression of the stabilizing protein microtubule‐associated protein tau or decreased expression of the destabilizing protein stathmin is associated with better outcome in breast cancer.