Endothelial proliferation, neoangiogenesis, and potential de novo generation of cerebrovascular malformations

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Object. To date, both arteriovenous malformations (AVMs) and cavernomas have been considered to be congenital malformations. A recent survey of the literature has shown the potential for de novo generation of both familial and sporadic cavernomas as well as AVMs. Therefore, it was of interest to determine the biological behavior of these lesions in detail.

Methods. The proliferative and angiogenic capacities of the endothelium of 13 cavernomas and 25 AVMs obtained in patients recently treated (1997–1998) at one institution were studied. Immunohistochemical staining for proliferating cell nuclear antigen (PCNA), MIB-1, and vascular endothelial growth factor (VEGF) and its receptor Flk-1 was performed using standard staining procedures. Positive immunostaining of the nuclei of endothelial cells was observed in specimens of both AVMs and cavernomas for PCNA (80% of AVMs and 85% of cavernomas), and Flk-1 (80% of AVMs and 31% of cavernomas). Endothelial expression of VEGF in the 18 incompletely embolized AVMs was found in 72% of cases but only in 28% of the seven cases in which patients did not undergo endovascular treatment; it was found in 38% of cavernomas. Endothelial expression of MIB-1 was found in 12% of AVMs but in no cavernomas.

Conclusions. These results indicate that there is endothelial proliferation as well as neoangiogenesis in cerebral cavernomas and AVMs. The increased level of angiogenesis in only partially obliterated AVMs underscores the need for radical and complete occlusion of cerebral AVMs to avoid recurrences and further risks of morbidity.

Article Information

Address reprint requests to: Ulrich Sure, M.D., Department of Neurosurgery, Philipps University, Baldingerstrasse, 35033 Marburg, Germany. email: sure@post.med.uni-marburg.de.

© AANS, except where prohibited by US copyright law.

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    A—E: Photomicrographs of AVM specimens subjected to immunohistochemical staining for different antibodies, showing nuclear expression of MIB-1 (A), PCNA (B and C), VEGF (D), and the Flk-1 antibody (E) within the endothelial cells. Original magnification × 2000 (A), × 1000 (B, C, and D), and × 400 (E). F and G: Photomicrographs of cavernoma specimens that had been subjected to immunohistochemical staining for different antibodies, showing expression of Flk-1 in the endothelium (F) and positive endothelial immunostaining for VEGF (G). Original magnification × 400.

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