ALTERED DISTRIBUTION OF KERATINIZATION MARKERS IN EPIDERMOLYTIC HYPERKERATOSIS

Epidermolytic hyperkeratosis (EH) is a genetic disorder of keratins as sociated with epidermal differentiation. Affected individuals carry ge ne mutations for conserved sequences of keratins K1 or K10. The struct ural alterations of tonofilaments in EH seem to be a direct consequenc e of the keratin gene mutations, EH epidermis, however, shows many oth er unexplained abnormalities including acanthosis, hypergranulosis, an d hyperkeratosis. To further elucidate the pathogenetic mechanism of E H, we studied distribution patterns of other keratinization-associated molecules including involucrin, small proline-rich protein (SPRR) 1, loricrin and trichohyalin in the skin of four patients by light and el ectron microscopic immunohistochemistry in conjunction with convention al transmission electron microscopy. The middle to upper epidermal cel ls showed moderate to strong immunoreactivities to involucrin, SPRR1 a nd loricrin antibodies. Both intracellular staining and cell periphera l staining was seen for involucrin and SPRR1 antibodies. Loricrin labe lling was prematurely associated with the plasma membrane of granular cells, possibly relating to abnormal keratin filament aggregation and cellular vacuolization. Some loricrin labelling was localized on the k eratin aggregates, suggesting intermolecular associations between kera tin and loricrin. Trichohyalin, hardly detectable in normal epidermis, was present in some granular and cornified cells in EH in association with keratin filaments, suggesting that it may function as an interme diate filament-associated protein. While cornified cell envelopes were intensely labelled only with loricrin antibodies in normal skin, they were immunoreactive to involucrin, SPRR1 and loricrin antibodies in E H. Sequential change in electron density of the cornified cell envelop es, a constant feature in normal skin, was often absent in EH. These r esults suggest an altered assembly process of cornified cell envelopes in EH.