Quantitatively determined survivin expression levels are of prognostic value in human gliomas.
OBJECTIVE
Survivin is a novel antiapoptotic gene that has been recently cloned and characterized. Its expression has been found to be of prognostic significance in several tumor types. This is the first study on the prognostic significance of survivin expression in human gliomas.


METHODS
We used quantitative Western blot analysis with densitometry to determine survivin protein expression levels in 92 glioma cases for which frozen tissue was available for analysis. Survivin positivity and expression levels were correlated with histopathologic features of the tumors, apoptosis (as measured by cleaved, or activated, caspase 3 levels), and clinical outcome.


RESULTS
Survivin expression has clear prognostic value in human gliomas. Patients with detectable survivin expression had significantly shorter overall survival times (P <.0001) compared with those without detectable expression when all glioma patients were considered. Although glioblastoma multiforme (GBM) patients had significantly higher rates of survivin positivity and higher levels of survivin expression (P <.0001) than their non-GBM counterparts, the prognostic value of survivin expression seemed to be independent of histology alone. Survivin-positive GBM patients had significantly shorter overall survival times compared with survivin-negative GBM patients (P <.0001). Likewise, survivin-positive non-GBM patients had shorter survival times compared with survivin-negative non-GBM patients (P =.029). Furthermore, increasing levels of survivin expression significantly correlated with reduced survival times when all glioma patients were considered, and markedly so for GBM patients (P <.0001). Increasing survivin levels significantly correlated with reduced expression of cleaved caspase 3, indicating its association with antiapoptotic activity.


CONCLUSIONS
Survivin positivity and protein expression levels, as determined quantitatively, are of significant prognostic value in human gliomas and seem to be associated with reduced apoptotic capacity of these tumors.
Chakravarti
Arnab
A
Department of Radiation Oncology, Massachusetts General Hospital Cancer Center, Boston, MA 02129, USA. achakravarti@partners.org
Noll
Elizabeth
E
Black
Peter McL
PM
Finkelstein
Daniel F
DF
Finkelstein
Dianne M
DM
Dyson
Nicholas J
NJ
Loeffler
Jay S
JS
D000328:Adult; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis / Q000096:biosynthesis*; D015853:Cysteine Proteinase Inhibitors / Q000032:analysis / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis; D000077022:Survivin
C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D002868:Chromosomal Proteins, Non-Histone; D015853:Cysteine Proteinase Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin