Immunohistochemical evidence for Zic1 coexpression with -catenin in the myofibroblast of Dupuytren disease

The active cellular component in Dupuytren disease (DD) is the -smooth muscle actin (-SMA) containing myofibroblast. The underlying regulatory processes in activation of myofibroblasts resemble the pathophysiology of certain types of cancer. Accumulation of -catenin has been shown in many fibroproliferative processes, including DD and, recent findings attributed a possible role to the Zic1 transcription factor. To assess Zic1 expression in DD and investigate its relation with the accumulation of -catenin, neighbouring tissue samples in 20 patients with DD were stained immunohistochemically with monoclonal antibodies for -catenin, -SMA, and Zic1. Histological appearance was staged according to Luck. Cell-rich areas with accumulation of -catenin in myofibroblasts that stained for -SMA and showed apparent Zic1 coexpression were obvious. This coexpression seemed independent of proliferative or involutional histological staging. We found only Zic1 expression in residual stages. A different pattern of expression of protein in the residual stage may support earlier suggestions of a cellular heterogeneity with the existence of different cell (sub-)populations in nodules and cords. On the other hand coexpression of Zic1 and -catenin may indicate a relation between Zic1 and the Wnt-pathway. Further studies are needed to elucidate cellular origin, potential heterogeneity and activity of the myofibroblasts in DD, and to define the exact role of Zic1 in fibroproliferative processes, wound healing, and cancer. The fibroblast in DD is an interesting model for future experiments.