Survivin subcellular localization in high-grade astrocytomas: simultaneous expression in both nucleus and cytoplasm is negative prognostic marker.
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.
Saito
Taiichi
T
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
Arifin
Muhamad Thohar
MT
Hama
Seiji
S
Kajiwara
Yoshinori
Y
Sugiyama
Kazuhiko
K
Yamasaki
Fumiyuki
F
Hidaka
Toshikazu
T
Arita
Kazunori
K
Kurisu
Kaoru
K
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
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