Annals of Oncology Advance Access originally published online on January 10, 2006
Annals of Oncology 2006 17(4):597-604; doi:10.1093/annonc/mdj121
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© 2006 European Society for Medical Oncology
Survivin expression in breast cancer predicts clinical outcome and is associated with HER2, VEGF, urokinase plasminogen activator and PAI-1
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 and 4 Department of Biomathematics and Biostatistics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA; 3 Departments of Obstetrics and Gynecology, Klinikum Grosshadern, Ludwig Maximilians Universität München, München, Germany; 5 Genentech, South San Francisco, California; 6 Department of Gynecologic Surgery, Mayo Clinic Foundation, Rochester, Minnesota; Departments of 7 Medical Oncology and 8 Nuclear Medicine and Medical Oncology, St Vincent's University Hospital, Dublin, Ireland
* Correspondence to: B. Ryan, Education and Research Centre, St Vincent's University Hospital, Dublin 4, Ireland. Tel: +353-1-209-4936; Fax: +353-1-283-8123; E-mail: Brid.Ryan{at}ucd.ie
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.
Key words: breast cancer, HER2, prognosis, survivin, uPA/PAI-1, VEGF
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