Journal of Clinical Oncology, Vol 19, Issue 4
(February), 2001: 992-1000
© 2001 American Society for Clinical Oncology
BAG-1: A Novel Biomarker Predicting Long-Term Survival in Early-Stage Breast Cancer
By Bruce C. Turner,
Stanislaw Krajewski,
Maryla Krajewska,
Shinichi Takayama,
Andrew A. Gumbs,
Darryl Carter,
Timothy R. Rebbeck,
Bruce G. Haffty,
John C. Reed
From Thomas Jefferson University, Department of Radiation Oncology and Kimmel Cancer Center; University of Pennsylvania School of Medicine, Department of Epidemiology and Biostatistics, Philadelphia, PA; The Burnham Institute, La Jolla, CA; and Yale University School of Medicine, Departments of Therapeutic Radiology and Pathology, New Haven, CT.
Address reprint requests to John C. Reed, MD, PhD, The Burnham Institute, 10901 North Torrey Pines Rd, La Jolla, CA 92037; email: jreed{at}burnham.org
PURPOSE: Among women with early-stage breast cancer treated with lumpectomy and radiation therapy, 30% to 40% will develop metastatic disease, which is often fatal. A need exists therefore for biomarkers that distinguish patients at high risk of relapse. We performed a retrospective correlative analysis of BAG-1 protein expression in breast tumors derived from a cohort of early-stage breast cancer patients.
PATIENTS AND METHODS: Archival paraffin blocks from 122 women with stages I to II breast cancer treated with lumpectomy and radiation therapy (median follow-up, 12.1 years) were analyzed by immunohistochemical methods using monoclonal antibodies recognizing BAG-1 and other biomarkers, including Bcl-2, estrogen receptor, progesterone receptor, p53, and HER2/Neu. Immunostaining data were correlated with distant metastasis-free survival (DMFS) and overall survival (OS).
RESULTS: Cytosolic immunostaining for BAG-1 was upregulated in 79 (65%) of 122 invasive breast cancers (P < .001) compared with normal breast. Elevated BAG-1 was significantly associated with longer DMFS and OS, overall (stages 1 and II) and in node-negative (stage I only) patients, on the basis of univariate and multivariate analyses (DMFS, P = .005; OS, P = .01, in multivariate analysis of all patients; DMFS, P = .005; OS, P = .001, in multivariate analysis of node-negative patients). All other biomarkers failed to reach statistical significance in multivariate analysis. Clinical stage was an independent predictor of OS (P = .04) and DMFS (P = .02).
CONCLUSION: These findings provide preliminary evidence that BAG-1 represents a potential marker of improved survival in early-stage breast cancer patients, independent of the status of axillary lymph nodes.
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Facebook  Reddit  Technorati  Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
N. K. Clemo, T. J. Collard, S. L. Southern, K. D. Edwards, M. Moorghen, G. Packham, A. Hague, C. Paraskeva, and A. C. Williams
BAG-1 is up-regulated in colorectal tumour progression and promotes colorectal tumour cell survival through increased NF-{kappa}B activity
Carcinogenesis,
April 1, 2008;
29(4):
849 - 857.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Y. Pandya, L. I. Talley, A. R. Frost, T. J. Fitzgerald, V. Trivedi, M. Chakravarthy, D. C. Chhieng, W. E. Grizzle, J. A. Engler, H. Krontiras, et al.
Nuclear Localization of KLF4 Is Associated with an Aggressive Phenotype in Early-Stage Breast Cancer
Clin. Cancer Res.,
April 15, 2004;
10(8):
2709 - 2719.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Krajewska, S. Krajewski, S. Banares, X. Huang, B. Turner, L. Bubendorf, O.-P. Kallioniemi, A. Shabaik, A. Vitiello, D. Peehl, et al.
Elevated Expression of Inhibitor of Apoptosis Proteins in Prostate Cancer
Clin. Cancer Res.,
October 15, 2003;
9(13):
4914 - 4925.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. A. Townsend, R. I. Cutress, A. Sharp, M. Brimmell, and G. Packham
BAG-1 Prevents Stress-induced Long-term Growth Inhibition in Breast Cancer Cells via a Chaperone-dependent Pathway
Cancer Res.,
July 15, 2003;
63(14):
4150 - 4157.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. J. Hung, R. S. Roberson, J. Taft, and D. Y. Wu
Human BAG-1 Proteins Bind to the Cellular Stress Response Protein GADD34 and Interfere with GADD34 Functions
Mol. Cell. Biol.,
May 15, 2003;
23(10):
3477 - 3486.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Schmidt, G. M. Wochnik, M. C. Rosenhagen, J. C. Young, F. U. Hartl, F. Holsboer, and T. Rein
Essential Role of the Unusual DNA-binding Motif of BAG-1 for Inhibition of the Glucocorticoid Receptor
J. Biol. Chem.,
February 7, 2003;
278(7):
4926 - 4931.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. C. Turner, M. Ottey, D. B. Zimonjic, M. Potoczek, W. W. Hauck, E. Pequignot, C. L. Keck-Waggoner, C. Sevignani, C. M. Aldaz, P. A. McCue, et al.
The Fragile Histidine Triad/Common Chromosome Fragile Site 3B Locus and Repair-deficient Cancers
Cancer Res.,
July 15, 2002;
62(14):
4054 - 4060.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Kudoh, D. A. Knee, S. Takayama, and J. C. Reed
Bag1 Proteins Regulate Growth and Survival of ZR-75-1 Human Breast Cancer Cells
Cancer Res.,
March 1, 2002;
62(6):
1904 - 1909.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Sjostrom, C. Blomqvist, K. von Boguslawski, N.-O. Bengtsson, I. Mjaaland, P. Malmstrom, B. Ostenstadt, E. Wist, V. Valvere, S. Takayama, et al.
The Predictive Value of bcl-2, bax, bcl-xL, bag-1, fas, and fasL for Chemotherapy Response in Advanced Breast Cancer
Clin. Cancer Res.,
March 1, 2002;
8(3):
811 - 816.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. I. Cutress, P. A. Townsend, A. C. Bateman, P.W.M. Johnson, K. Ryder, D. M. Barnes, G. Packham, B. C. Turner, and J. C. Reed
BAG-1 Immunostaining and Survival in Early Breast Cancer
J. Clin. Oncol.,
August 15, 2001;
19(16):
3706 - 3707.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Parton, M. Dowsett, and I. Smith
Studies of apoptosis in breast cancer
BMJ,
June 23, 2001;
322(7301):
1528 - 1532.
[Full Text]
[PDF]
|
|
|
|
