title: Stathmin expression and its relationship to microtubule-associated protein tau and outcome in breast cancer.
abstract: 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.
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Baquero
authors.forename: Jason A
authors.initials: JA
authors.lastname: Hanna
authors.forename: Veronique
authors.initials: V
authors.lastname: Neumeister
authors.forename: Huan
authors.initials: H
authors.lastname: Cheng
authors.forename: Annette M
authors.initials: AM
authors.lastname: Molinaro
authors.forename: Lyndsay N
authors.initials: LN
authors.lastname: Harris
authors.forename: David L
authors.initials: DL
authors.lastname: Rimm
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D001940:Breast / Q000737:chemistry; D001943:Breast Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D015331:Cohort Studies; D005260:Female; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D034741:RNA, Small Interfering / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors; D050777:Stathmin / Q000032:analysis*; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D016875:tau Proteins / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D034741:RNA, Small Interfering; D050777:Stathmin; D016875:tau Proteins