Vascular endothelial growth factor expression in oligodendrogliomas: a correlative study with Sainte-Anne malignancy grade, growth fraction and patient survival.
Microangiogenesis is a delayed but crucial event in the malignant progression of oligodendrogliomas. Accord-ingly, in the new Sainte-Anne grading system of oligodendrogliomas, endothelial hyperplasia and contrast enhancement, both being indicators of microangiogenesis, are key criteria for the distinction of grade A from grade B tumours. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor: a strong correlation between VEGF expression, Sainte-Anne malignancy grade and patient outcome might thus be expected. In order to assess this hypothesis, VEGF immunostaining was performed in a series of 34 oligodendrogliomas that included 11 grade B and 23 grade A, of which nine became grade B during the study period (mean clinical and imaging follow-up: 41 months). VEGF expression correlated strongly with Sainte-Anne tumour grade (P < 0.001), and inversely with patient survival (P < 0.001) and recurrence-free survival (P = 0.002). One hundred per cent of grade B but only 17% of grade A were VEGF-positive. By contrast, the MIB-1 labelling index did not correlate with VEGF expression, total survival or recurrence-free survival. In accordance with the grading system, this study showed that, in oligodendrogliomas, VEGF expression and microangiogenesis are progression-related phenomena that confer on these tumours a growth advantage by presumably reducing hypoxia-induced apoptotic cell death. These findings might have important implications in the future for the indication and timing of anti-angiogenic therapies.
Department of Pathology-Neurooncology, Hôpital Sainte-Anne, Paris, France.
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P
Varlet
J S
JS
Guillamo
F
F
Nataf
M
M
Koziak
F
F
Beuvon
C
C
Daumas-Duport
D000328:Adult; D000368:Aged; D034961:Antigens, Nuclear; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D002455:Cell Division; D018572:Disease-Free Survival; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen; D008222:Lymphokines / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D009687:Nuclear Proteins; D009837:Oligodendroglioma / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D016016:Proportional Hazards Models; D013223:Statistics as Topic; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D034961:Antigens, Nuclear; D016228:Endothelial Growth Factors; D019394:Ki-67 Antigen; D008222:Lymphokines; D009687:Nuclear Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors