title: Clinical progression and familial occurrence of cerebral cavernous angiomas: the role of angiogenic and growth factors.
abstract: OBJECTIVE
  The authors studied the expression of angiogenic and growth factors and various proliferative indices in cavernous angiomas of the brain. The goal was to define whether the often progressive clinical course of both sporadic and familial forms of the lesion is correlated with different expression of these factors.
  
  
  METHODS
  Forty-three cavernomas of the brain were investigated with immunohistochemical studies and stained for four growth factors (vascular endothelial growth factor [VEGF], tenascin, transforming growth factor-b [TGFb], and platelet-derived growth factor [PDGF]), and for Ki-67 and bcl-2. The intensity of expression was tested in all cases in the walls of cavernoma vessels, in the perivascular tissue, and in the perilesional brain parenchyma. Among the 43 cavernomas, 32 were stable and sporadic single lesions less than 2 cm in size, whereas 11 were cavernomas larger than 2 cm (up to 6 cm). These larger cavernomas had more aggressive behavior (documented growth in five cases, mass effect in eight, significant hemorrhage in four), familial occurrence (six cases), and/or multiple lesions (five cases). The expression of VEGF, tenascin, and PDGF in cavernomas did not significantly differ in the two groups of patients, whereas TGFb expression was higher in the more aggressive forms of cavernomas. The expression of Ki-67 and bcl-2 was always absent in stable lesions, and it was positive in eight (72.7%) of 11 aggressive lesions. The perilesional brain parenchyma showed a significantly higher expression of TGFb, PDGF, and tenascin in more aggressive cavernomas.
  
  
  CONCLUSIONS
  The familial occurrence and more aggressive clinical behavior of cavernous angiomas of the brain are associated with higher expression of Ki-67 and bcl-2 in the cavernoma tissue, as in other proliferative lesions. These features are also associated with higher expression of some growth factors (excluding VEGF) in the perilesional brain parenchyma, suggesting that the neighboring vasculature and glia may be predisposed to and recruited for further growth and progression.
authors.affiliation: Division of Neurosurgery, Department of Neurological Sciences, Università degli Studi di Napoli Federico II, Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Maiuri
authors.forename: Paolo
authors.initials: P
authors.lastname: Cappabianca
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Gangemi
authors.forename: Marialaura Del Basso
authors.initials: Mdel B
authors.lastname: De Caro
authors.forename: Felice
authors.initials: F
authors.lastname: Esposito
authors.forename: Guido
authors.initials: G
authors.lastname: Pettinato
authors.forename: Oreste
authors.initials: O
authors.lastname: de Divitiis
authors.forename: Chiara
authors.initials: C
authors.lastname: Mignogna
authors.forename: Viviana
authors.initials: V
authors.lastname: Strazzullo
authors.forename: Enrico
authors.initials: E
authors.lastname: de Divitiis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D002550:Cerebral Veins / Q000002:abnormalities / Q000473:pathology / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism*; D020786:Hemangioma, Cavernous, Central Nervous System / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D019063:Tenascin / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042501:Angiogenic Proteins; D006133:Growth Substances; D019394:Ki-67 Antigen; D010982:Platelet-Derived Growth Factor; D019253:Proto-Oncogene Proteins c-bcl-2; D019063:Tenascin; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A