Against the rules: human keratin K80: two functional alternative splice variants, K80 and K80.1, with special cellular localization in a wide range of epithelia.

Of the 54 human keratins, five members have, at present, only been characterized at the gene level. In this study we have investigated the expression patterns of keratin K80, whose gene is located at the centromeric end of the type II keratin gene domain. K80 possesses a number of highly unusual properties. Structurally, it is distinctly closer to type II hair keratins than to type II epithelial keratins. Nonetheless, it is found in virtually all types of epithelia (stratified keratinizing/non-keratinizing, hard-keratinizing, as well as non-stratified tissues, and cell cultures thereof). This conspicuously broad expression range implies an unprecedented in vivo promiscuity of K80, which involves more than 20 different type I partners for intermediate filament (IF) formation. Throughout, K80 expression is related to advanced tissue or cell differentiation. However, instead of being part of the cytoplasmic IF network, K80 containing IFs are located at the cell margins close to the desmosomal plaques, where they are tightly interlaced with the cytoplasmic IF bundles abutting there. In contrast, in cells entering terminal differentiation, K80 adopts the "conventional" cytoplasmic distribution. In evolutionary terms, K80 is one of the oldest keratins, demonstrable down to fish. In addition, KRT80 mRNA is subject to alternative splicing. Besides K80, we describe a smaller but fully functional splice variant K80.1, which arose only during mammalian evolution. Remarkably, unlike the widely expressed K80, the expression of K80.1 is restricted to soft and hard keratinizing epithelial structures of the hair follicle and the filiform tongue papilla.

The keratins of the human beard hair medulla: the riddle in the middle.

We have investigated the expression of 52 of the 54 keratins in beard hair medulla. We found that not only 12 hair keratins but, unexpectedly, also 12 epithelial keratins are potentially expressed in medulla cells. The latter comprise keratins also present in outer- and inner-root sheaths and in the companion layer. Keratins K5, K14, K17, K25, K27, K28, and K75 define a "pre-medulla," composed of cells apposed to the upper dermal papilla. Besides K6, K16, K7, K19, and K80, all pre-medullary epithelial keratins continue to be expressed in the medulla proper, along with the 12 hair keratins. Besides this unique feature of cellular keratin co-expression, the keratin pattern itself is highly variable in individual medulla cells. Remarkably, both epithelial and hair keratins behave highly promiscuously with regard to heterodimer- and IF formation, which also includes keratin chain interactions in IF bundles. We also identified cortex cells within the medullary column. These exhibit all the properties of genuine cortex cells, including a particular type of keratin heterogeneity of their compact IF bundles. In both keratin expression profile and keratin number, medulla cells are distinct from all other cells of the hair follicle or from any other epithelium.

Ameloblastoma, calcifying epithelial odontogenic tumor, and glandular odontogenic cyst show a distinctive immunophenotype with some myoepithelial antigen expression.

BACKGROUND: Odontogenic neoplasms have some morphologic overlap with salivary gland neoplasms, many of which show myoepithelial differentiation. In the 1980s, an ultrastructural study identified a population of myoepithelial-like cells in calcifying epithelial odontogenic tumor. Myoepithelial derived tumors have since been shown to have distinct immunohistochemical profiles. METHODS: We examined a series of odontogenic neoplasms, including 11 ameloblastomas, four calcifying epithelial odontogenic tumors, five glandular odontogenic cysts (GOCs), and five keratocystic odontogenic tumors with a panel of myoepithelial-associated immunohistochemical stains. We also assessed representative control examples of oral mucosa, odontogenic rests, and dentigerous cysts. RESULTS: All of the neoplastic and non-neoplastic oral epithelium-derived entities share a p63-positive, high molecular weight cytokeratin (CK5/6)-positive immunophenotype. Calponin reactivity was at least focally present in two of four calcifying epithelial odontogenic tumors, three of five GOCs, and 10 of 11 ameloblastomas; the sole completely non-reactive ameloblastoma represents a lung metastasis. One case of calcifying epithelial odontogenic tumor was focally positive for glial fibrillary acidic protein. However, other more definitive markers of myoepithelial differentiation, including S-100 and smooth muscle actin, were negative. Two of three calcifying epithelial odontogenic tumors and five of five GOCs were also positive for a low molecular weight cytokeratin (CK7). CONCLUSIONS: Ameloblastomas, GOCs, and calcifying epithelial odontogenic tumors show a distinctive immunophenotype which overlaps with that of myoepithelial-derived salivary gland neoplasms but does not provide definitive support for myoepithelial differentiation.