Conflict of interest: Nothing to declare.
BIRC5 expression is a poor prognostic marker in Ewing sarcoma†
Version of Record online: 7 SEP 2012
Copyright © 2012 Wiley Periodicals, Inc.
Pediatric Blood & Cancer
Volume 60, Issue 1, pages 35–40, January 2013
How to Cite
Hingorani, P., Dickman, P., Garcia-Filion, P., White-Collins, A., Kolb, E. A. and Azorsa, D. O. (2013), BIRC5 expression is a poor prognostic marker in Ewing sarcoma. Pediatr. Blood Cancer, 60: 35–40. doi: 10.1002/pbc.24290
- Issue online: 15 NOV 2012
- Version of Record online: 7 SEP 2012
- Manuscript Accepted: 22 JUL 2012
- Manuscript Received: 11 JAN 2012
- Phoenix Children's Hospital Foundation
- Ewing sarcoma;
- targeted therapy
BIRC5 (Survivin), an inhibitor of apoptosis protein (IAP), is over-expressed in several human cancers and increased expression is associated with poor prognosis. The goal of the current study was to evaluate the role of BIRC5 in Ewing sarcoma (ES), the second most common pediatric bone sarcoma.
BIRC5 protein expression was determined in ES cell lines using Western Blot analysis. Functional role of survivin on growth and viability of ES cells was assessed by siRNA knockdown of BIRC5 and by using a small molecule inhibitor YM155. Immunohistochemical analysis for BIRC5 protein was performed on patient tumor samples using an anti-survivin antibody. The degree of BIRC5 protein expression was correlated with clinical parameters and patient outcome.
BIRC5 is over-expressed in a panel of ES cell lines. Gene silencing of BIRC5 in the ES cell line TC-71 decreases cell growth by more than 50% for each BIRC5 siRNA construct compared to non-silencing siRNA control constructs. YM155 also reduces ES cell growth and viability with an EC50 ranging from 2.8 to 6.2 nM. BIRC5 protein is expressed in majority of the ES tumor samples with minimal expression in normal tissue (P < 0.005). Tumors with more than 50% expression are associated with worse overall survival than tumors with less than 50% expression (Hazard Ratio: 6.05; CI: 1.7–21.4; P = 0.04).
BIRC5 is over-expressed in ES cell lines and tumor samples. Further, it plays an important role in cell growth and viability in vitro. Higher degree of expression in patients is an independent poor prognostic factor. Pediatr Blood Cancer 2013; 60: 35–40. © 2012 Wiley Periodicals, Inc.