Further Study of CD31 Protein and Messenger Ribonucleic Acid Expression in Human Cerebral Vascular Malformations

Abstract

In a previous study, we documented lower levels of immunoexpression of platelet endothelial cell (EC) adhesion molecule (CD31) in paraffin sections of cerebral cavernous malformations (CCMs), compared with arteriovenous malformations (AVMs) or normal brain tissue. We hypothesized that down-regulation of CD31 in CCMs might represent a distinctive phenotypic feature of ECs in this disease. To confirm this hypothesis, we further examined both protein and messenger ribonucleic acid (mRNA) expression of CD31, using immunohistochemical and in situ hybridization analyses, in fresh-frozen specimens of CCMs, AVMs, and control brain tissue. Fresh-frozen sections of four AVMs, five CCMs, and four control brain tissue specimens obtained from surgical resections were immunohistochemically stained with antibodies to von Willebrand factor and two distinct epitopes of CD31. In two AVMs, four CCMs, and three control brain tissue samples from the aforementioned group, the expression of CD31 mRNA was also examined by using in situ hybridization. Large (>100-microm) and small (<100-microm) vessels were counted and assessed for protein and mRNA expression. In all tissues, ECs in the majority of vessels were immunopositive for CD31 with two distinct antibodies. CD31 mRNA was expressed in some but not all vessels in AVMs, CCMs, and control brain tissue. There were no statistically significant differences in CD31 protein or mRNA expression in CCMs, AVMs, and control brain tissue. The expression of CD31 in CCMs can be underestimated in paraffin sections. There does not seem to be a unique phenotypic differentiation of CD31 expression in ECs of CCMs or AVMs, compared with control brain tissue.