Expression of endothelial cell angiogenesis receptors in human cerebrovascular malformations

OBJECTIVE: To further understand the role of angiogenic growth factors in t he development of cerebral cavernous malformations (CCMs) and arteriovenous malformations (AVMs), we investigated endothelial cell (EC) expression of receptors for vascular endothelial growth factor (VEGF) and angiopoietin sy stems in patients with surgically resected lesions. METHODS: Paraffin-embedded sections of five AVMs, CCMs, and normal control brain tissue samples were stained immunohistochemically with antibodies to von Willebrand factor and CD31 (to characterize ECs) and angiogenesis growt h factor receptors Flt-1 (VEGF-R1), Flk-1 (VEGF-R2), Tie-1, and Tie-2. We c ounted large and small vessels in each specimen, assessed each specimen's i mmunoexpression of each antigen, and analyzed differences between CCMs, AVM s, and the normal control brain tissue samples. RESULTS: The ECs of CCMs, AVMs, and normal control brain tissue samples exp ressed the von Willebrand factor uniformly, but the ECs of CCMs were largel y negative for CD31 (P < 0.05). Flk-1, Flt-1, and Tie-2 were not expressed in the control brain tissue samples. The proportion of immunopositive vesse ls to VEGF receptors Flk-1 and Flt-1 was significantly greater in AVMs and CCMs than in the control brain tissue samples (P < 0.05). Tie-2 in AVMs and CCMs was expressed in a higher percentage of immunopositive vessels than i n the control brain tissue samples, but the difference was not statisticall y significant. Tie-1 was expressed in rare vessels of all lesion types and control brain tissue samples. CONCLUSION: ECs of CCMs do not seem to express CD31 to the same extent that AVMs and normal brain tissue do. AVMs and CCMs show greater expression of VEGF receptors, but not of angiopoietin receptors, than normal brain tissue does.