Tight junctions (TJs), hallmark structures of one-layered epithelia and of endothelia, are of central biological importance as intramembranous "fences" and as hydrophobic "barriers" between lumina represented by liquid- or gas-filled spaces on the one hand and the mesenchymal space on the other. They have long been thought to be absent from stratified epithelia. Recently, however, constitutive TJ proteins and TJ-related structures have also been identified in squamous stratified epithelia, including the epidermis, where they occur in special positions, most prominently in the uppermost living epidermal cell layer, the stratum granulosum. Much to our surprise, however, we have now also discovered several major TJ proteins (claudins 1 and 4, occludin, cingulin, symplekin, protein ZO-1) and TJ-related structures in specific positions of formations of epithelium-derived tissues that lack any lumen and do not border on luminal or body surfaces. Using immunohistochemistry and electron microscopy we have localized TJ proteins and structures in peripheral cells of the Hassall's corpuscles of human and bovine thymi as well as in specific central formations of tumor nests in squamous cell carcinomas, including the so-called "horn pearls". Such structures have even been found in carcinoma metastases. In carcinomas, they often seem to separate certain tumor regions from others or from stroma. The structural significance and the possible functional relevance of the locally restricted synthesis of TJ proteins and of the formations of TJ-related structures are discussed. It is proposed to include the determination of the presence or absence of such proteins and structures in the diagnostic program of tumor pathology.
