Tight junction-associated proteins (occludin, ZO-1, claudin-1, claudin-4) in squamous cell carcinoma and Bowen's disease

Background The epidermis, which is a typical stratified epithelium, has tight junctions (TJs) in the granular layer, as do simple epithelia. So far, abnormalities of TJs and involvement of claudin-1 have been reported in tumours of simple epithelia. Objectives To examine the expression of TJ-associated proteins (occludin, ZO-1, claudin-1 and claudin-4) in normal human epidermis and in malignant disorders of keratinization. Methods Expression of the proteins in normal human epidermis, five cases of squamous cell carcinoma (SCC) of the skin and five cases of Bowen's disease (BD) was examined by immunofluorescence staining. Results In normal human epidermis, occludin, ZO-1 and claudin-4 were expressed at the cell-cell borders in the granular layer specifically or dominantly, whereas claudin-1 was expressed in the whole epithelium. In SCC, occludin, ZO-1, claudin-1 and claudin-4 were strongly expressed in tumour cells with keratinization such as cancer pearls. Claudin-1 was heterogeneously expressed in unkeratinized tumour cells, whereas expression of occludin, ZO-1 and claudin-4 was decreased or absent. In BD, aberrant expression of occludin, ZO-1, claudin-1 and claudin-4 was observed at the cell-cell borders in addition to their expression patterns observed in normal epidermis. Conclusions Expression of occludin, ZO-1 and claudin-4 is associated with keratinization in SCC and BD. However, the heterogeneous expression of claudin-1 in SCC is not determined only by keratinization.