Survivin, Survivin-2B, and Survivin-deItaEx3 expression in medulloblastoma: biologic markers of tumour morphology and clinical outcome.

• Type of Material: Article
• Authors: Jason Fangusaro, Emory University; Y Jiang, The Ohio State University; MP Holloway, The Ohio State University; H Caldas, The Ohio State University; V Singh, The Ohio State University; DR Boue, The Ohio State University; J Hayes, The Ohio State University; RA Altura, The Ohio State University
• Language: English
• Date: 2005-01-31
• Publisher: Cancer Research UK
• Publication Version: Final Published Version
• Copyright Statement: © 2005 Cancer Research UK.
• License: Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1038/sj.bjc.6602317
• Title of Journal or Parent Work: British Journal of Cancer
• ISSN: 0007-0920
• Volume: 92
• Issue: 2
• Start Page: 359
• End Page: 365
• Grant/Funding Information: This work has been generously funded by an institutional T-32 NIH research Grant (T32 HD043003-02) and by the Elsa U Pardee Foundation.
• Keywords: Life Sciences & Biomedicine; SPINDLE CHECKPOINT; Oncology; medulloblastoma; Science & Technology; apoptosis; NERVOUS-SYSTEM; Survivin; LARGE CELL/ANAPLASTIC MEDULLOBLASTOMAS; SPLICE VARIANTS; PEDIATRIC-ONCOLOGY-GROUP; RADIATION-THERAPY; PROGNOSTIC-FACTORS; Survivin isoforms; APOPTOSIS; BRAIN-TUMORS; CANCER

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-deltaExB, 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.