Analysis of Phosphorylated MEK1 Expression Pattern in Cutaneous Dilated Vessels of Capillary Malformations

The mechanism of capillary malformation (CM) is thought to be the abnormal dilation of capillaries as a result of activation of the RAS-RAF-MEK-ERK pathway due to GNAQ/GNA11 gene mutations. However, no prior studies have actually demonstrated phosphorylation of MEK in CM. CMs were classified into three types according to clinical and histopathological findings: Flat, hypertrophic, and nodular. Comparison of the expression pattern of phosphorylated MEK1 (p-MEK1) in these three types of CMs revealed that p-MEK1 staining was positive in dilated capillaries in the upper dermis of the flat CMs. Double staining was performed to determine which cells of CM expressed p-MEK1: CD34 and p-MEK1 showed partial co-localization, demonstrating that p-MEK1 is expressed in the vascular endothelial cells. Both p-MEK1-positive and p-MEK1-negative vessels were observed in dilated vessels of CM. In addition, p-MEK1-positive vessels may be present deeper than anticipated. JNK and ERK were also phosphorylated in the dilated vessels. Furthermore, in contrast to the flat type and hypertrophic type of CM, the nodular type showed no p-MEK1 expression in its proliferated capillaries, supporting the notion that nodular CMs arise via a distinct mechanism. Taken together, our results indicated that visualization of affected vessels of CM using p-MEK1 immunostaining is useful not only for diagnosis but also for understanding the pathogenesis of CM.