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 differ- entiated adult tissues. Elevated survivin levels are found in malignant systemic tumors, and are associated with chemo-resistance, radiation resistance, and poor progno- sis. However, expression of survivin in primary nervous system tumors has not been previously characterized. Im- munohistochemistry using anti-human survivin antibody (SURV11-A) was performed on formalin-fixed, paraffin- embedded archival tissue from 112 primary central ner- vous 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 pleo- morphic xanthoastrocytoma (1) were positive to a lesser degree. In oligodendrogliomas (6) and mixed oligo-astro- cytomas [grade II (5), II–III (3), and III (7)], oligoden- droglial elements appear to be negative compared to pos- itive mini-gemistocytic oligodendrocytes. Ependymomas [grade II (6) and grade III (1)] were positive. Medul- loblastomas (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 neurofibro- mas (6) were intensely positive. Thus, survivin is ex- pressed in the majority of the primary nervous system tumors, particularly in glioblastomas, meningiomas, schwannomas and neurofibromas. Overexpression of sur- vivin in meningiomas and benign peripheral nerve sheath tumors contrasts with previous reports relating it to rapid division and poor prognosis. Keywords Tumor · Survivin · Apoptosis protein inhibitor · Caspase inhibitor · Brain tumor Introduction Survivin is a member of the family of inhibitors of apop- tosis protein (IAP). It is located on chromosome 17q25. The coding strand of the survivin gene is highly similar to the sequence of effector cell protease receptor-1 (EPR-1), but in the opposite direction [5]. Survivin is expressed in the G2-M phase of the cell cycle, and is associated with mitotic spindles [16]. It initiates cell cycle entry as a result of nuclear translocation followed by an interaction with Cdk4. Overexpression of survivin results in an acceler- ated S-phase shift, resistance to G1 arrest, and Cdk2/cy- clin E activation and Rb phosphorylation. Survivin trans- location into the nucleus is dependent on Fas stimulation and cell proliferation. As a result of the survivin/Cdk4 complex formation, p21 is released from its complex with Cdk4 and interacts with mitochondrial procaspase 3 to suppress Fas-mediated cell death [25, 26]. The ubiquitin- proteosome pathway regulates survivin degradation in a cell-cycle-dependent manner [30]. Recently, survivin was also reported to function as a kinetochore-associated pas- senger protein [24]. The anti-apoptotic function of survivin has been ex- plained by its ability to block the terminal effector cell- death proteases, caspases-3 and -7, but not the proximal Tsutomu Sasaki · M. Beatriz S. Lopes · Gerald R. Hankins · Gregory A. Helm Expression of survivin, an inhibitor of apoptosis protein, in tumors of the nervous system Acta Neuropathol (2002) 104 : 105–109 DOI 10.1007/s00401-002-0532-x Received: 30 June 2001 / Revised: 8 November 2001 / Accepted: 15 January 2001 / Published online: 29 March 2002 REGULAR PAPER Portions of this work were presented at the 16th International Conference on Brain Tumor Research and Therapy, May 2001, and the 51st Annual Meeting of the Congress of Neurological Surgeons, October 2001. T. Sasaki (✉) · G.R. Hankins Department of Neurosurgery, University of Virginia, Charlottesville, VA 22908, USA e-mail: ts5k@virginia.edu, Tel.: +1-434-9242203, Fax: +1-434-9249242 M.B.S. Lopes Department of Pathology, Division of Neuropathology, University of Virginia, Charlottesville, Virginia, USA G.A. Helm Departments of Neurosurgery and Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA © Springer-Verlag 2002