Biological activity of adult cavernous malformations: a study of 56 patients.
OBJECTIVE
Cerebral cavernous malformations (CCMs) have previously been considered as congenital and biologically static malformations. On the other hand, the potential for growth and de novo generation of CCMs have also been reported. It is therefore important to study the proliferative and neoangiogenetic capacity of these lesions.


METHODS
The authors studied the surgical specimens of 56 CCMs (23 deep and 33 superficial) obtained from adult patients. The proliferative activity of the endothelium and the neoangiogenetic capacity of these lesions were considered through immunohistochemical anaylsis of proliferating cell nuclear antigen (PCNA), MIB-1, Flk-1, vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF)-1alpha, and endoglin antibodies. Positive immunostaining of endothelial cells occurred in 86% of patients for PCNA and in 38% of the cases for MIB 1. The expression of Flk-1 was observed in the endothelium of 71% of the cases, for VEGF in 41%, for HIF-1 alpha in 48.1%, and for endoglin in 63.6% of the cases. The correlation of immunohistochemical and clinical data indicated that VEGF was expressed in significantly less deep-seated lesions when compared with superficial CCMs. Neither the expression of the proliferative markers nor the expression of the angiogenetic antibodies correlated with patient age at surgery, sex, or the number of recent prior hemorrhagic episodes in the patients.


CONCLUSIONS
The CCMs from adult patients are active lesions exhibiting endothelial proliferation and neoangiogenesis. According to the data in this study, neoangiogenesis is more prominent in superficial CCMs than in deep-seated CCMs and is not associated with recent prior hemorrhages.
Sure
Ulrich
U
Department of Neurosurgery, Philipps University, Marburg, Germany. sure@med.uni-marburg.de
Freman
Sandra
S
Bozinov
Oliver
O
Benes
Ludwig
L
Siegel
Adrian M
AM
Bertalanffy
Helmut
H
D000328:Adult; D000368:Aged; D015703:Antigens, CD; D001921:Brain / Q000473:pathology / Q000601:surgery; D001932:Brain Neoplasms / Q000473:pathology* / Q000601:surgery; D002455:Cell Division / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D004268:DNA-Binding Proteins / Q000032:analysis; D000071063:Endoglin; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D006392:Hemangioma, Cavernous / Q000473:pathology* / Q000601:surgery; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000601:surgery; D009687:Nuclear Proteins / Q000032:analysis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011956:Receptors, Cell Surface; D013223:Statistics as Topic; D014157:Transcription Factors / Q000032:analysis; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis
D015703:Antigens, CD; D004268:DNA-Binding Proteins; C064206:ENG protein, human; D000071063:Endoglin; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2