Survivin expression and its relation with proliferation, apoptosis, and angiogenesis in brain gliomas

BACKGROUND An unbalance of cell proliferation and cell apoptosis is an important mechanism in carcinogenesis, and angiogenesis also plays a crucial role in tumorigenesis. Recently, survivin has been identified as an important member of the inhibitor of apoptosis protein (IAP) family. Although it has been shown that survivin is highly expressed in gliomas, and is associated with tumorigenesis, progression, and poor prognosis of gliomas, as yet the relation of survivin expression with proliferation, apoptosis, and angiogenesis of gliomas it is still unclear. METHODS Eighty-three cases of brain glioma were chosen and protein expressions of survivin and proliferating cell nuclear antigen (PCNA) in glioma cells and Factor VIII-related antigen (FVIII-RAg) in vascular endothelial cells were investigated by immunohistochemistry. Apoptotic cells of brain glioma were screened by TdT-mediated dUTP nick end-labeling (TUNEL), and survivin immunoreactivity score (IRS), proliferative index (PI), apoptotic index (AI), overall daily growth (ODG), and microvessel density (MVD) in brain gliomas were measured. RESULTS The survivin IRS, PI, AI, ODG, and MVD of brain gliomas were 3.75 ± 3.89, 28.39 ± 19.49%, 1.00 ± 0.80%, 12.19 ± 10.21%, and 62.75 ± 31.50, respectively, and all of them increased markedly with an increase in the pathologic grade of brain gliomas (P < 0.001 for all). PI, ODG, and MVD in the survivin-positive group were significantly higher than those in the survivin-negative group (P < 0.001 for all). PI, ODG, and MVD were positively correlated with survivin IRS (P < 0.001 for all). Although there was no significant difference between AI in the survivin-positive group or in the survivin-negative group (P = 0.108), AI was inversely correlated with survivin IRS (P = 0.005). CONCLUSIONS Survivin is overexpressed in brain gliomas, which may play an important role in malignant proliferation, antiapoptosis, and angiogenesis of brain gliomas. Cancer 2005. © 2005 American Cancer Society.