Abstract Basal keratins, suprabasal keratins, filag- grin, and cornified cell envelope (CCE) precursor pro- teins are expressed during the differentiation of epi- dermal keratinocytes. These molecules are coordi- nately expressed during epidermal differentiation. The present study investigated the expression patterns of keratins and CCE precursor proteins in 15 patients with epidermolysis bullosa simplex (EBS), which is caused by mutations in the genes that encode for the basal keratins, keratins 5 and 14. The patterns of ex- pression of keratins 5, 14, 1 and 10, filaggrin, and of the three major CCE precursor proteins, involucrin, lori- crin and small proline-rich proteins 1 and 2 (SPRs), were studied immunohistochemically and by electron microscopy. In 14 of the 15 patients with EBS, the dis- tribution pattern of keratins was not altered. In one neonate with EBS, basal cell keratins were expressed in the suprabasal layers. Ultrastructurally, numerous clumped tonofilaments were observed in the basal and suprabasal cells. In all cases, findings were positive for filaggrin in the granular cells, with positivity for in- volucrin in the upper spinous and granular cells. The upper spinous cells and granular cells were positive for SPRs 1 and 2, and loricrin was expressed in granu- lar cells. Ultrastructurally, no marked abnormality was observed in the suprabasal layers such as a decrease in, or agglutination of, keratin filaments, except in one neonate. A CCE about 15 nm thick was formed nor- mally in the cell membrane of cornified cells. The pat- terns of distributions of basal cell keratins, suprabasal keratins, filaggrin, and CCE precursor proteins, as well as the ultrastructural findings, resembled those of nor- mal skin. Thus, the abnormality in basal cell keratins in patients with EBS did not appear to alter the pat- terns of expression of the keratins and CCE precursor proteins. Key words Keratin · Epidermolysis bullosa simplex · Cornified cell envelope Introduction The keratins, which are the major structural proteins of the keratinocytes, are important in maintaining the func- tion of the skin. The process of keratinization is initiated by the expression of keratins 5 (K5) and 14 (K14) in the basal cells, and terminates with the production of horny cells in which filaggrin and the cornified cell envelope (CCE) precursor proteins play important roles. Thus, it seems that mutations in the basal keratin gene could lead to the abnormal expression of keratin and the filaggrin fil- ament network that could lead to a defect in CCE produc- tion. Based on electron microscopic finding of an abnor- mal organization of keratin intermediate filaments in cul- tured epidermal keratinocytes of epidermolysis bullosa simplex (EBS) [18], mutations of the keratin gene in pa- tients with EBS were first reported in 1991 [1, 7]. Many other groups have since reported similar gene mutations [2, 3, 5, 6, 10, 11, 19, 21, 29]. However, only a few stud- Yuko Sasaki · Hiroshi Shimizu · Masashi Akiyama · Kozo Yoneda · Akemi Ishida-Yamamoto · Shinichi Watanabe · Junichi Hata · Takeji Nishikawa Abnormalities of basal cell keratin in epidermolysis bullosa simplex do not affect the expression patterns of suprabasal keratins and cornified cell envelope proteins Arch Dermatol Res (1998) 290 : 591–597 © Springer-Verlag 1998 Received: 8 April 1998 / Received after revision: 17 July 1998 / Accepted: 30 July 1998 ORIGINAL PAPER Y. Sasaki (Y) · H. Shimizu · T. Nishikawa Department of Dermatology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan Tel. +81-3-3353-1211, ext. 2413; Fax +81-3-3351-6880; e-mail: yuko@mc.med.keio.ac.jp M. Akiyama Division of Dermatology, Kitasato Institute Hospital, Tokyo, Japan K. Yoneda Department of Dermatology, Kyoto University Faculty of Medicine, Kyoto, Japan A. Ishida-Yamamoto Department of Dermatology, Asahikawa Medical College, Asahikawa, Japan S. Watanabe Department of Dermatology, Teikyo University School of Medicine, Tokyo, Japan J. Hata Department of Pathology, Keio University School of Medicine, Tokyo, Japan