title: Expression of survivin, an inhibitor of apoptosis protein, in tumors of the nervous system.
abstract: Survivin is an inhibitor of apoptosis protein that blocks apoptosis by binding to caspases-3 and -7. It is highly expressed in less-differentiated embryonic cells and rapidly dividing tumors, but not in terminally differentiated adult tissues. Elevated survivin levels are found in malignant systemic tumors, and are associated with chemo-resistance, radiation resistance, and poor prognosis. However, expression of survivin in primary nervous system tumors has not been previously characterized. Immunohistochemistry using anti-human survivin antibody (SURV11-A) was performed on formalin-fixed, paraffin-embedded archival tissue from 112 primary central nervous system tumors. Survivin immunoreactivity was seen in most diffuse astrocytomas [WHO II (2/4), III (3/3), IV (9/10), giant-cell glioblastoma (1), and gliosarcoma (1)]. The intensity and degree of survivin expression showed trends with tumor grade, with glioblastomas having the highest positivity. Pilocytic astrocytomas (5) and pleomorphic xanthoastrocytoma (1) were positive to a lesser degree. In oligodendrogliomas (6) and mixed oligo-astrocytomas [grade II (5), II-III (3), and III (7)], oligodendroglial elements appear to be negative compared to positive mini-gemistocytic oligodendrocytes. Ependymomas [grade II (6) and grade III (1)] were positive. Medulloblastomas (5) and retinoblastoma (1/4) showed focal positivity. All meningiomas [grade I (12), II (9), III (4), and grade I (3) and II (5) with frank brain invasion] were intensely positive. All schwannomas (11) and neurofibromas (6) were intensely positive. Thus, survivin is expressed in the majority of the primary nervous system tumors, particularly in glioblastomas, meningiomas, schwannomas and neurofibromas. Overexpression of survivin in meningiomas and benign peripheral nerve sheath tumors contrasts with previous reports relating it to rapid division and poor prognosis.
authors.affiliation: Department of Neurosurgery, University of Virginia, Charlottesville 22908, USA. ts5k@virginia.edu
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sasaki
authors.forename: M Beatriz S
authors.initials: MB
authors.lastname: Lopes
authors.forename: Gerald R
authors.initials: GR
authors.lastname: Hankins
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Helm
mesh_terms: D001254:Astrocytoma / Q000737:chemistry*; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000737:chemistry*; D002528:Cerebellar Neoplasms / Q000737:chemistry; D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis* / Q000276:immunology; D004806:Ependymoma / Q000737:chemistry; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008527:Medulloblastoma / Q000737:chemistry; D008577:Meningeal Neoplasms / Q000737:chemistry; D008579:Meningioma / Q000737:chemistry; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009837:Oligodendroglioma / Q000737:chemistry; D011379:Prognosis; D019572:Retinal Neoplasms / Q000737:chemistry; D012175:Retinoblastoma / Q000737:chemistry; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D002868:Chromosomal Proteins, Non-Histone; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin