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Quantitatively Determined Survivin Expression Levels Are of Prognostic Value in Human Gliomas

From the Departments of Radiation Oncology and Biostatistics and Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, and Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA.

Address reprint requests to Arnab Chakravarti, MD, Massachusetts General Hospital, Laboratory of Molecular Oncology, 13th St, Bldg 149, Room 7330, Charlestown, MA 02129; email: achakravarti@ partners.org.

PURPOSE: 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.

MATERIALS AND 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.

CONCLUSION: 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.

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