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Received on June 24, 2004
Accepted on August 6, 2004
Molecular Diagnostics and Genetics |
1 Department of Chemical Endocrinology, University Medical Center Nijmegen, Nijmegen, The Netherlands, and Chemical Endocrinology.
2 Department of Clinical Chemistry, University Medical Center Nijmegen, Nijmegen, The Netherlands, and Chemical Endocrinology.
3 Department of Medical Oncology, University Medical Center Nijmegen, Nijmegen, The Netherlands, and Chemical Endocrinology.
4 Departments of Chemical Endocrinology and Medical Oncology, University Medical Center Nijmegen, Nijmegen, The Netherlands.
* To whom correspondence should be addressed. E-mail: p.span{at}ace.umcn.nl.
Background: Results in previous qualitative studies of the association of the apoptosis inhibitor survivin with prognosis of breast cancer patients have been contradictory.
Methods: Survivin mRNA was measured by quantitative TaqMan reverse transcription-PCR in 275 breast cancer tissues from patients with operable tumors and was correlated with established clinicopathologic factors, relapse-free survival [(RFS); 102 events], and overall survival [(OS); 81 events].
Results: High survivin mRNA concentrations were found mainly in tissues from younger patients and in high-grade cancer tissues. High survivin concentrations were most strongly associated with estrogen receptor- or progesterone receptor-negative tumors. In univariate Cox regression analysis for RFS, survivin concentrations were significantly associated with poor prognosis with a hazard ratio (HR) of 1.99 (95% confidence interval, 1.31-3.02; P = 0.001) for every 10-fold increase in expression. For OS, a significant contribution of survivin to poor prognosis was found with a HR of 2.76 (1.67-4.55; P <0.001). Multivariate analyses were performed including established clinicopathologic factors. For RFS, age (P = 0.027), nodal category (P <0.001), and survivin [HR = 1.78 (1.18-2.68); P = 0.006] contributed significantly to the model. For OS, only nodal category (P <0.001) and survivin [HR = 3.05 (1.83-5.10); P <0.001] were significant.
Conclusion: Survivin demonstrates a strong, independent, association with poor prognosis. Survivin might be used as a new marker to stratify breast cancer patients for more optimal treatment modalities, or it could be a promising new target for therapy.
The following articles in journals at HighWire Press have cited this article:
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  G. Giaccone, P. Zatloukal, J. Roubec, K. Floor, J. Musil, M. Kuta, R. J. van Klaveren, S. Chaudhary, A. Gunther, and S. Shamsili Multicenter Phase II Trial of YM155, a Small-Molecule Suppressor of Survivin, in Patients With Advanced, Refractory, Non-Small-Cell Lung Cancer J. Clin. Oncol., September 20, 2009; 27(27): 4481 - 4486. [Abstract] [Full Text] [PDF]
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A. W. Tolcher, A. Mita, L. D. Lewis, C. R. Garrett, E. Till, A. I. Daud, A. Patnaik, K. Papadopoulos, C. Takimoto, P. Bartels, et al. Phase I and Pharmacokinetic Study of YM155, a Small-Molecule Inhibitor of Survivin J. Clin. Oncol., November 10, 2008; 26(32): 5198 - 5203. [Abstract] [Full Text] [PDF]
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 C. Shen, L. Hu, L. Xia, and Y. Li Quantitative Real-time RT-PCR Detection for Survivin, CK20 and CEA in Peripheral Blood of Colorectal Cancer Patients Jpn. J. Clin. Oncol., November 1, 2008; 38(11): 770 - 776. [Abstract] [Full Text] [PDF]
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 D. J. Brennan, E. Rexhepaj, S. L. O'Brien, E. McSherry, D. P. O'Connor, A. Fagan, A. C. Culhane, D. G. Higgins, K. Jirstrom, R. C. Millikan, et al. Altered Cytoplasmic-to-Nuclear Ratio of Survivin Is a Prognostic Indicator in Breast Cancer Clin. Cancer Res., May 1, 2008; 14(9): 2681 - 2689. [Abstract] [Full Text] [PDF]
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 P. N. Span, V. C.G. Tjan-Heijnen, J. J.T.M. Heuvel, J. B. de Kok, J. A. Foekens, and F. C.G.J. Sweep Do the Survivin (BIRC5) Splice Variants Modulate or Add to the Prognostic Value of Total Survivin in Breast Cancer? Clin. Chem., September 1, 2006; 52(9): 1693 - 1700. [Abstract] [Full Text] [PDF]
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 M. Lacroix, R.-A. Toillon, and G. Leclercq p53 and breast cancer, an update. Endocr. Relat. Cancer, June 1, 2006; 13(2): 293 - 325. [Abstract] [Full Text] [PDF]
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 K. W. Rahman, Y. Li, Z. Wang, S. H. Sarkar, and F. H. Sarkar Gene Expression Profiling Revealed Survivin as a Target of 3,3'-Diindolylmethane-Induced Cell Growth Inhibition and Apoptosis in Breast Cancer Cells. Cancer Res., May 1, 2006; 66(9): 4952 - 4960. [Abstract] [Full Text] [PDF]
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 S. Fukuda and L. M. Pelus Survivin, a cancer target with an emerging role in normal adult tissues Mol. Cancer Ther., May 1, 2006; 5(5): 1087 - 1098. [Abstract] [Full Text] [PDF]
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 B. M. Ryan, G. E. Konecny, S. Kahlert, H.-J. Wang, M. Untch, G. Meng, M. D. Pegram, K. C. Podratz, J. Crown, D. J. Slamon, et al. Survivin expression in breast cancer predicts clinical outcome and is associated with HER2, VEGF, urokinase plasminogen activator and PAI-1 Ann. Onc., April 1, 2006; 17(4): 597 - 604. [Abstract] [Full Text] [PDF]
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H. Asanuma, T. Torigoe, K. Kamiguchi, Y. Hirohashi, T. Ohmura, K. Hirata, M. Sato, and N. Sato Survivin Expression Is Regulated by Coexpression of Human Epidermal Growth Factor Receptor 2 and Epidermal Growth Factor Receptor via Phosphatidylinositol 3-Kinase/AKT Signaling Pathway in Breast Cancer Cells Cancer Res., December 1, 2005; 65(23): 11018 - 11025. [Abstract] [Full Text] [PDF]
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