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.