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.
Zhen
Hai-Ning
HN
Institute of Neurosurgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, The People's Republic of China.
Zhang
Xiang
X
Hu
Pei-Zhen
PZ
Yang
Tong-Tao
TT
Fei
Zhou
Z
Zhang
Jian-Ning
JN
Fu
Luo-An
LA
He
Xiao-Sheng
XS
Ma
Fu-Cheng
FC
Wang
Xi-Ling
XL
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology; D014408:Biomarkers, Tumor / Q000032:analysis; D001707:Biopsy, Needle; D001932:Brain Neoplasms / Q000473:pathology* / Q000503:physiopathology; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005910:Glioma / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000378:metabolism*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D011237:Predictive Value of Tests; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D000077022:Survivin
C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin