Evaluation of prognostic and predictive value of microtubule associated protein tau in two independent cohorts

Breast Cancer Research

David L Rimm³  Lyndsay N Harris⁴  Annette M Molinaro²  Robert L Camp³  Franck Appia¹  Kimberly A Bassi¹  Mark D Gustavson⁶  Karen Lostritto⁵  Maria T Baquero³ 

[1] Sanofi-Aventis, International Clinical Trial Management/Oncology, 200 Crossing Blvd. Bridgewater, NJ 08807, USA;Yale University School of Medicine, Department of Epidemiology and Public Health, 500 College St, New Haven, CT 06511, USA;Yale University School of Medicine, Department of Pathology, 310 Cedar St, New Haven, CT 06520, USA;Yale University School of Medicine, Department of Clinical Oncology, 333 Cedar Street, New Haven, CT 06510, USA;Yale University School of Medicine, Department of Computational Biology, 333 Cedar Street, New Haven, CT 06510, USA;HistoRx, 35 Northeast Industrial Road, Branford, Connecticut, 06405, USA

关键词: immunohistochemistry;    quantitative analysis;    predictive;    prognostic;    taxanes;    metastatic breast cancer;    microtubule associated protein- tau (MAP-tau);   

Others  :  799139
DOI  :  10.1186/bcr2937

 received in 2011-03-04, accepted in 2011-11-02,  发布年份 2011

【 摘 要 】

Introduction

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.

【 授权许可】

   
2011 Baquero et al.; licensee BioMed Central Ltd.

【 图 表 】

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