title: Biological activity of adult cavernous malformations: a study of 56 patients.
abstract: 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.
authors.affiliation: Department of Neurosurgery, Philipps University, Marburg, Germany. sure@med.uni-marburg.de
authors.forename: Ulrich
authors.initials: U
authors.lastname: Sure
authors.forename: Sandra
authors.initials: S
authors.lastname: Freman
authors.forename: Oliver
authors.initials: O
authors.lastname: Bozinov
authors.forename: Ludwig
authors.initials: L
authors.lastname: Benes
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Siegel
authors.forename: Helmut
authors.initials: H
authors.lastname: Bertalanffy
mesh_terms: 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
chemical_list: 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