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

Maria T Baquero,Annette M Molinaro,Karen Lostritto,Franck Appia,David L Rimm,Robert L Camp,Mark D Gustavson,Lyndsay N Harris,Kimberly A Bassi

doi:10.1186/bcr2937

Maria T Baquero, Annette M Molinaro + Show 7 more

Open Access

https://doi.org/10.1186/bcr2937

Copy DOI

Abstract

IntroductionMicrotubule 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.MethodsMAP-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.ResultsAssessment 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).ConclusionsQuantitative 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.

Highlights

Microtubule associated proteins (MAPs) endogenously regulate microtubule stabilization and have been reported as prognostic and predictive markers for taxane response
microtubule associated protein- tau (MAP-tau) expression and distribution In order to establish a cutpoint that could be used to differentiate high versus low MAP-tau expression in patients, MAP-tau was measured in normal epithelial ducts and lobules in tissue microarray (TMA) format (n = 220)
The median MAP-tau expression score in normal breast tissue was subsequently used in all analyses to differentiate high expressers (AQUA score ≥ 462) from low expressers

Summary

Introduction

Microtubule associated proteins (MAPs) endogenously regulate microtubule stabilization and have been reported as prognostic and predictive markers for taxane response. Microtubule associated proteins (MAPs) are endogenous regulators of microtubule stability, functioning to promote or inhibit microtubule polymerization and determining subsequent cell cycle progression or mitotic arrest. In the NSABP-B 28 randomized clinical trial, there was no prediction of benefit from paclitaxel but high MAP-tau expression was a positive prognostic marker for improved survival [12]. Two additional studies of advanced breast cancer patients found high MAP-tau expression predictive for response to paclitaxel [14,15] and a positive prognostic marker for improved overall survival [15]

Objectives

Methods

Results

Discussion

Conclusion