title: Evaluation of prognostic and predictive value of microtubule associated protein tau in two independent cohorts.
abstract: BACKGROUND
  Microtubule associated proteins (MAPs) endogenously regulate microtubule stabilization and have been reported as prognostic and predictive markers for taxane response. The microtubule stabilizer, MAP-tau, has shown conflicting results. We quantitatively assessed MAP-tau expression in two independent breast cancer cohorts to determine prognostic and predictive value of this biomarker.
  
  
  METHODS
  MAP-tau expression was evaluated in the retrospective Yale University breast cancer cohort (n = 651) using tissue microarrays and also in the TAX 307 cohort, a clinical trial randomized for TAC versus FAC chemotherapy (n = 140), using conventional whole tissue sections. Expression was measured using the AQUA method for quantitative immunofluorescence. Scores were correlated with clinicopathologic variables, survival, and response to therapy.
  
  
  RESULTS
  Assessment of the Yale cohort using Cox univariate analysis indicated an improved overall survival (OS) in tumors with a positive correlation between high MAP-tau expression and overall survival (OS) (HR = 0.691, 95% CI = 0.489-0.974; P = 0.004). Kaplan Meier analysis showed 10-year survival for 65% of patients with high MAP-tau expression compared to 52% with low expression (P = .006). In TAX 307, high expression was associated with significantly longer median time to tumor progression (TTP) regardless of treatment arm (33.0 versus 23.4 months, P = 0.010) with mean TTP of 31.2 months. Response rates did not differ by MAP-tau expression (P = 0.518) or by treatment arm (P = 0.584).
  
  
  CONCLUSIONS
  Quantitative measurement of MAP-tau expression has prognostic value in both cohorts, with high expression associated with longer TTP and OS. Differences by treatment arm or response rate in low versus high MAP-tau groups were not observed, indicating that MAP-tau is not associated with response to taxanes and is not a useful predictive marker for taxane-based chemotherapy.
authors: Yale University School of Medicine, Department of Pathology, 310 Cedar St, New Haven, CT 06520, USA.
authors: Maria T
authors: MT
authors: Baquero
authors: Karen
authors: K
authors: Lostritto
authors: Mark D
authors: MD
authors: Gustavson
authors: Kimberly A
authors: KA
authors: Bassi
authors: Franck
authors: F
authors: Appia
authors: Robert L
authors: RL
authors: Camp
authors: Annette M
authors: AM
authors: Molinaro
authors: Lyndsay N
authors: LN
authors: Harris
authors: David L
authors: DL
authors: Rimm
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000627:therapeutic use; D003593:Cytoplasm / Q000378:metabolism; D000077143:Docetaxel; D004317:Doxorubicin / Q000627:therapeutic use; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D015996:Survival Rate; D043823:Taxoids / Q000627:therapeutic use; D016875:tau Proteins / Q000032:analysis* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C054369:MAPT protein, human; D043823:Taxoids; D016875:tau Proteins; D000077143:Docetaxel; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil