title: Survivin, Survivin-2B, and Survivin-deItaEx3 expression in medulloblastoma: biologic markers of tumour morphology and clinical outcome.
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.
authors.affiliation: Center 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.
authors.forename: J R
authors.initials: JR
authors.lastname: Fangusaro
authors.forename: Y
authors.initials: Y
authors.lastname: Jiang
authors.forename: M P
authors.initials: MP
authors.lastname: Holloway
authors.forename: H
authors.initials: H
authors.lastname: Caldas
authors.forename: V
authors.initials: V
authors.lastname: Singh
authors.forename: D R
authors.initials: DR
authors.lastname: Boué
authors.forename: J
authors.initials: J
authors.lastname: Hayes
authors.forename: R A
authors.initials: RA
authors.lastname: Altura
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002528:Cerebellar Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002648:Child; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008527:Medulloblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000235:genetics; D009363:Neoplasm Proteins; D016133:Polymerase Chain Reaction; D011379:Prognosis; D020033:Protein Isoforms / Q000096:biosynthesis; D011995:Recombination, Genetic; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D000077022:Survivin