Claudin-1 expression decreases with increasing pathological grade in actinic keratosis and may be a marker of high-risk actinic keratosis

Abstract

Background Actinic keratosis (AK) is a common sun-induced skin disorder that can progress to invasive squamous cell carcinoma. However, there is still no reliable method to predict high-risk AK. Aim To identify markers that reflect the biological behaviour of AK and to understand the pathogenesis of AK. Methods In total, 52 patients with AK and 17 site-matched healthy controls (HCs) were enrolled. We evaluated solar elastosis and immunohistochemical features using antibodies to p53, vitamin D receptor (VDR), claudin-1 and Langerin (CD207). Comparisons between AK and HC skin were performed and analyses carried out according to the pathological grade of AK. Results We found that in both patients and HCs, solar elastosis increased and Langerhans cell (LC) density decreased with ageing. Solar elastosis and p53 expression were higher and VDR expression was lower in patients than in HCs; however, there was no statistical difference between them in relation to the pathological grade of AK. Claudin-1 expression gradually decreased from HC skin to severe AK, and particularly decreased in areas with epidermal atypia. LC density in severe AK was significantly lower than in HC skin and mild AK, while there was no difference in LC density between HC skin, mild AK and moderate AK. Conclusions Claudin-1 could be a useful marker of the pathological severity of AK. In addition, p53 increases and VDR decreases in AK, not in a gradual manner but in the early steps of carcinogenesis. LC density is relatively maintained in AK until it reaches severe dysplasia.