title: Survivin subcellular localization in high-grade astrocytomas: simultaneous expression in both nucleus and cytoplasm is negative prognostic marker.
abstract: OBJECTIVE
  Subcellularly localized (nuclear and/or cytoplasmic) survivin has various functions, and correlates with prognosis of malignant tumors. However, there have been no reports about the significance of subcellularly localized survivin in high-grade astrocytomas. The aim of the present study was to examine the relationship between prognosis and subcellular localization of survivin in high-grade astrocytoma.
  
  
  METHODS
  We immunohistochemically examined the pattern of subcellular localization of survivin expression (nuclear, cytoplasmic, or both) in 51 patients with high-grade astrocytoma (19 anaplastic astrocytomas; 32 glioblastomas). We statistically examined the relationship between survivin localization and prognosis, using multivariate analysis including other clinicopathological factors (age, sex, WHO grade, extent of resection, MIB-1 labeling index, and expression of p53 and epidermal growth factor receptor).
  
  
  RESULTS
  All specimens stained positive for survivin: localized in nucleus only (nuclear-positive group), 10 cases (20%); localized in cytoplasm only (cytoplasmic-positive group), 23 cases (45%); simultaneous expression in nucleus and cytoplasm (nuclear-cytoplasmic group), 19 cases (35%). There was no significant difference in prognosis between the nuclear-positive group and cytoplasmic-positive group (P=0.796). However, the nuclear-cytoplasmic group had significantly shorter overall survival than the nuclear-positive group and the cytoplasmic-positive group (P<0.0001).
  
  
  CONCLUSIONS
  We found that simultaneous expression of survivin in both the nucleus and cytoplasm is an important prognostic factor for high-grade astrocytoma. The present findings indicate that subcellular localization of survivin expression is a reliable prognostic factor for patients with this tumor.
authors.affiliation: Department of Neurosurgery, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. taiichi@hiroshima-u.ac.jp
authors.forename: Taiichi
authors.initials: T
authors.lastname: Saito
authors.forename: Muhamad Thohar
authors.initials: MT
authors.lastname: Arifin
authors.forename: Seiji
authors.initials: S
authors.lastname: Hama
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kajiwara
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Sugiyama
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Yamasaki
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Hidaka
authors.forename: Kazunori
authors.initials: K
authors.lastname: Arita
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kurisu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012189:Retrospective Studies; D013347:Subcellular Fractions; D015996:Survival Rate; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D066246:ErbB Receptors; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; C107489:BIRC5 protein, human; C064740:epidermal growth factor receptor-neu receptor