Biological activity of paediatric cerebral cavernomas: an immunohistochemical study of 28 patients.
OBJECTIVE
According to the hypothesis that paediatric cerebral cavernomas may have different biological activity compared to adult cavernomas, immunohistochemical analysis was used to elucidate the biological nature of paediatric cavernomas.


METHODS
We examined the histological features and the proliferative and angiogenic capacity of the tissue specimens acquired from 28 paediatric patients. Normal paediatric brain tissues obtained from paediatric autopsy cases were used as a control group. The proliferative activity of the endothelium and the neoangiogenetic capacity were investigated by immunohistochemistry for proliferating cell nuclear antigen (PCNA), Ki-67 epitope (MIB-1), Flk-1 receptor, vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF)-1 alpha, and endoglin antibody, respectively. Afterwards, the results of the paediatric lesions were analysed and compared with the correspondent values of previously reported immunohistochemical analysis in adult cavernomas.


RESULTS
Positive immunostaining of VEGF was detected significantly less in paediatric cavernomas compared to adult cases (p<0.05). In contrast, endoglin, a protein that is upregulated during an increased vascular shear stress, was expressed more often in paediatric cavernomas (p<0.05). Neither the expression of the PCNA nor the expression of the HIF-1alpha was found significantly different between paediatric and adult cavernomas. However, the positive immunoreaction for MIB-1 occurred more often in the paediatric cases (p<0.05).


CONCLUSIONS
The immunohistochemical study indicates that paediatric cavernomas are dynamic lesions. The VEGF/Flk-1 associated neoangiogenesis may play a minor role for the biology of paediatric cavernomas, while endoglin seems to act more prominently than previously thought, particularly for the biology of paediatric cavernomas.
Tirakotai
Wuttipong
W
Department of Neurosurgery, Philipps University, Baldingerstrasse, 35033, Marburg, Germany. sure@med.uni-marburg.de
Fremann
Sandra
S
Soerensen
Niels
N
Roggendorf
Wolfgang
W
Siegel
Adrian M
AM
Mennel
Hans Dieter
HD
Zhu
Yuan
Y
Bertalanffy
Helmut
H
Sure
Ulrich
U
D000293:Adolescent; D015703:Antigens, CD / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D000071063:Endoglin; D005260:Female; D006392:Hemangioma, Cavernous / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007150:Immunohistochemistry; D007223:Infant; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D011956:Receptors, Cell Surface; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2