Immunohistochemical staining showed that ZO-1 expression in the samples harboring CCM gene mutations was significantly lower than that in the control samples (p < 0.0001, t-test), whereas ZO-1 expression in the MAP3K3-mutant samples was not different from that in the control samples (p = 0.3810; t-test) (Figure 4A). This evidence concerns the gene MAP3K3 and cerebral cavernous malformation.