Prognostic implications of the subcellular localization of survivin in glioblastomas treated with radiotherapy plus concomitant and adjuvant temozolomide

J Neurosurg. 2018 Mar;128(3):679-684. doi: 10.3171/2016.11.JNS162326. Epub 2017 Apr 21.

Abstract

OBJECTIVE Currently, the standard treatment protocol for patients with newly diagnosed glioblastoma (GBM) includes surgery, radiotherapy, and concomitant and adjuvant temozolomide (TMZ). Various prognostic biomarkers for GBM have been described, including survivin expression. The aim of this study was to determine whether the subcellular localization of survivin correlates with GBM prognosis in patients who received the standard treatment protocol. METHODS The authors retrospectively examined the subcellular localization of survivin (nuclear, cytoplasmic, or both) using immunohistochemistry in 50 patients with GBM who had received the standard treatment. The relationship between survivin localization and overall survival (OS) was assessed with uni- and multivariate analyses including other clinicopathological factors (age, sex, Karnofsky Performance Scale [KPS] score, extent of resection, the use of second-line bevacizumab, O6-methylguanine-DNA methyltransferase [MGMT] status, and MIB-1 labeling index). RESULTS Log-rank tests revealed that patient age, KPS score, extent of resection, MGMT status, and survivin localization (p < 0.0001) significantly correlated with OS. Multivariate analysis indicated that patient age, MGMT status, and survivin localization significantly correlated with OS. Patients with nuclear localization of survivin had a significantly shorter OS than those in whom survivin expression was exclusively cytoplasmic (median OS 19.5 vs 31.7 months, respectively, HR 5.690, 95% CI 2.068-17.612, p = 0.0006). There was no significant difference in OS between patents whose survivin expression was exclusively nuclear or nuclear/cytoplasmic. CONCLUSIONS Nuclear expression of survivin is a factor for a poor prognosis in GBM patients. Subcellular localization of survivin can help to predict OS in GBM patients treated with the standard protocol.

Keywords: DC = dendritic cell; GBM = glioblastoma; KPS = Karnofsky Performance Scale; LI = labeling index; MGMT = O6-methylguanine-DNA methyltransferase; OS = overall survival; TMZ = temozolomide; glioblastoma; oncology; prognosis; siRNA = short interfering RNA; subcellular localization; survivin; temozolomide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Brain / metabolism
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / radiotherapy
  • Cell Nucleus / metabolism
  • Chemotherapy, Adjuvant
  • Combined Modality Therapy
  • Cytoplasm / metabolism
  • Female
  • Glioblastoma / drug therapy
  • Glioblastoma / metabolism*
  • Glioblastoma / mortality
  • Glioblastoma / radiotherapy
  • Humans
  • Male
  • Middle Aged
  • Neurons / metabolism*
  • Prognosis
  • Radiotherapy*
  • Retrospective Studies
  • Survival Rate
  • Survivin / metabolism*
  • Temozolomide / therapeutic use*
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Alkylating
  • Survivin
  • Temozolomide