Expression patterns and prognostic value of Bag-1 and Bcl-2 in breast cancer

Yasmine Nadler , Robert L Camp , Jennifer M Giltnane , Christopher Moeder , David L Rimm , Harriet M Kluger and Yuval Kluger

Breast Cancer Research 2008, 10:R35doi:10.1186/bcr1998


Published:	22 April 2008

Abstract (provisional)

Introduction

Bag-1 binds the anti-apoptotic mediator, Bcl-2, and enhances its activity. Bcl-2 and Bag-1 are associated with chemotherapy resistance in cancer cells. Drugs that target Bcl-2 are currently in clinical development. Our purpose was to study expression patterns of Bag-1 in a large cohort of breast tumors and assess the association with Bcl-2, ER, PR and Her2/neu, and other clinical/pathological variables.

Methods

Tissue microarrays containing primary specimens from 638 patients with 10-year follow-up were employed and expression of Bag-1, Bcl-2, ER, PR and Her2/neu were assessed using our automated quantitative analysis (AQUA) method; we used cytokeratin to define pixels as breast cancer (tumor mask) within the array spot, and measured biomarker expression within the mask using Cy5 conjugated antibodies.

Results

High Bcl-2 expression was associated with improved survival in the entire cohort and in the node-positive subset (P = 0.008 and P=0.002, respectively). High Bag-1 expression was associated with improved survival in the node-positive subset (P=0.006). On multivariable analysis, neither Bcl-2 nor Bag-1 retained their independence as prognostic markers. Strong associations were found between Bag-1, Bcl-2, ER and PR.

Conclusions

Bag-1 and Bcl-2 expression in breast tumors are associated with improved outcome and steroid receptor positivity. Evaluation of Bcl-2 and Bag-1 expression in breast cancer may identify a subset of patients with a favorable prognosis, who might not benefit from chemotherapy, or who might benefit from Bcl-2 targeting agents in addition to anti-hormonal therapy.