Skip Navigation



Annals of Oncology Advance Access published online on January 10, 2006
Annals of Oncology, doi:10.1093/annonc/mdj121
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
17/4/597    most recent
mdj121v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Ryan, B. M.
Right arrow Articles by Duffy, M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ryan, B. M.
Right arrow Articles by Duffy, M. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2006 European Society for Medical Oncology
Received September 12, 2005
Revised November 28, 2005
Accepted November 30, 2005

original article

Survivin expression in breast cancer predicts clinical outcome and is associated with HER2, VEGF, urokinase plasminogen activator and PAI-1

B. M. Ryan 1 *, G. E. Konecny 2, S. Kahlert 3, H.-J. Wang 4, M. Untch 3, G. Meng 5, M. D. Pegram 6, K. C. Podratz 7, J. Crown 8, D. J. Slamon 6, and M. J. Duffy 9

1 School of Medicine and Medical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland
2 Division of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, California, USA; Department of Gynecologic Surgery, Mayo Clinic Foundation, Rochester, Minnesota
3 Departments of Obstetrics and Gynecology, Klinikum Grosshadern, Ludwig Maximilians Universität München, München, Germany
4 Department of Biomathematics and Biostatistics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA
5 Genentech, South San Francisco, California
6 Division of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, California, USA
7 Department of Gynecologic Surgery, Mayo Clinic Foundation, Rochester, Minnesota
8 Department of Medical Oncology, St Vincent's University Hospital, Dublin, Ireland
9 School of Medicine and Medical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland; Department of Nuclear Medicine and Medical Oncology, St Vincent's University Hospital, Dublin, Ireland

* To whom correspondence should be addressed.
B. M. Ryan, E-mail: Brid.Ryan{at}ucd.ie


  Abstract

Background: Survivin, a novel inhibitor of apoptosis, is one of the most cancer-specific proteins identified to date. In this study we (a) evaluated the association between survivin and HER2, vascular endothelial growth factor (VEGF) and uPA/PAI-1 expression and (b) defined its effect on clinical outcome in a large breast cancer patient cohort.

Patients and methods: Survivin expression was measured by ELISA in primary breast cancer tissue extracts from 420 patients with long-term clinical follow-up.

Results: Survivin was detected in 378 (90%) of the 420 primary breast cancer cases. Increased survivin levels were significantly associated with high nuclear grade (P < 0.0001), negative hormone receptor status (P = 0.0028), HER2 overexpression (P = 0.0094), VEGF expression (P < 0.0001), high uPA (P = 0.0002) and PAI-1 levels (P = 0.0002). Using the 25th percentile (1.4 ng/mg) as a cut-off point, patients expressing elevated survivin had a significantly worse disease-free survival (DFS: P = 0.0007, RR 1.97) and overall survival (OS: P = 0.0009, RR 2.11) compared with patients expressing lower levels of survivin. In multivariate analysis, this prognostic value of survivin was independent of both traditional and novel clinicopathologic factors for both DFS (P = 0.0076, RR 1.72) and OS (P = 0.0155, RR 1.76).

Conclusions: The independent prognostic relevance of survivin, when combined with previous data from model systems implicating survivin in the inhibition of apoptosis, suggests that survivin may be a suitable target for future therapeutic strategies.

Keywords: breast cancer; HER2; prognosis; survivin; uPA/PAI-1; VEGF.

BMR and GEK contributed equally to this work.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
J. Lu, M. Tan, W.-C. Huang, P. Li, H. Guo, L.-M. Tseng, X.-h. Su, W.-T. Yang, W. Treekitkarnmongkol, M. Andreeff, et al.
Mitotic Deregulation by Survivin in ErbB2-Overexpressing Breast Cancer Cells Contributes to Taxol Resistance
Clin. Cancer Res., February 15, 2009; 15(4): 1326 - 1334.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
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]

Home page
 Molecular Cancer TherapeuticsHome page
K. M. Aird, X. Ding, A. Baras, J. Wei, M. A. Morse, T. Clay, H. K. Lyerly, and G. R. Devi
Trastuzumab signaling in ErbB2-overexpressing inflammatory breast cancer correlates with X-linked inhibitor of apoptosis protein expression
Mol. Cancer Ther., January 1, 2008; 7(1): 38 - 47.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.