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

Object. To date, both arteriovenous malformations (AVMs) and cavernomas hav e been considered to be congenital malformations. A recent survey of the li terature has shown the potential for de novo generation of both familial an d sporadic cavernomas as well as AVMs. Therefore, it was of interest to det ermine 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 prolifer ating cell nuclear antigen (PCNA), MIB-1, and vascular endothelial growth f actor (VEGF) and its receptor Flk-1 was performed using standard staining p rocedures. Positive immunostaining of the nuclei of endothelial cells was o bserved 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). Endothel ial expression of VEGF in the 18 incompletely embolized AVMs was found in 7 2% of cases but only in 28% of the seven cases in which patients did not un dergo endovascular treatment; it was found in 38% of cavernomas. Endothelia l 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 ne ed for radical and complete occlusion of cerebral AVMs to avoid recurrences and further risks of morbidity.