1. ¹Center for Childhood Cancer Research, Columbus Children's Research Institute (CCRI), College of Medicine and Public Health, The Ohio State University, 700 Children's Drive, Columbus, OH 43205, USA
2. ²Department of Pediatrics, College of Medicine and Public Health, The Ohio State University, Columbus, OH, USA
3. ³Center for Biopathology, Columbus Children's Research Institute, Columbus Children's Hospital and College of Medicine and Public Health, The Ohio State University, Columbus, OH, USA

Correspondence: Dr RA Altura, ^*E-mail: alturar@pediatrics.ohio-state.edu

Received 2 August 2004; Revised 19 October 2004; Accepted 8 November 2004; Published online 18 January 2005.

Abstract

Survivin is an apoptotic inhibitor that is expressed at high levels in a variety of malignancies. Survivin has four known alternative splice forms (Survivin, Survivin-2B, Survivin-deltaEx3, and Survivin-3B), and the recent literature suggests that these splice variants have unique functions and subcellular localisation patterns. We evaluated 19 fresh-frozen paediatric medulloblastomas for the expression of three Survivin isoforms by quantitative PCR. Survivin was most highly expressed when compared with normal cerebellar tissue. We also investigated Survivin protein expression in 40 paraffin-embedded paediatric medulloblastoma tumours by immunohistochemistry. We found a statistically significant association between the percentage of Survivin-positive cells and histologic subtype, with the large-cell-anaplastic variant expressing Survivin at higher levels than the classic subtype. We also found a statistically significant relationship between the percent of Survivin-positive cells in the tumours and clinical outcome, with higher levels of Survivin correlating with a worse prognosis. In summary, our study demonstrates a role for Survivin as a marker of tumour morphology and clinical outcome in medulloblastoma. Survivin may be a promising future prognostic tool and potential biologic target in this malignancy.