Changes In Cytokeratin Expression Research Articles

Ultrastructural and morphological analysis during progression of Bowen disease reveals a complex interplay between hyperkeratosis, cytokeratin expression, host immunity and amyloid deposition.

Bowen disease, one of the common skin cancers, is defined as squamous cell carcinoma in situ, characterized by atypical keratinocytes occupying the full thickness of the epidermis, and predominantly occurs on sun-protected skin. There is no existing data on the impact of tumour and immune cell interactions or cytokeratin expression on the pathology of Bowen disease. We analysed dynamic changes in cytokeratin expression and immune cell composition during the development and progression of Bowen disease. Analysis was performed using immunohistochemistry and electron microscopy for samples from 140 patients with Bowen disease and 20 patients with invasive squamous cell carcinoma. We evaluated cytokeratin expression, the number of infiltrating immune cells and amyloid deposition by immunohistochemistry, and the ultrastructural relationship between tumour cells and immune cells by electron microscopy. The results showed that the expression of CK14 is associated with tumour progression, keratotic status and amyloid deposition and that the expression of CK10 is associated with accumulation of immune cells in Bowen disease. The findings of electron microscopy indicated repeated battles involving immune cells in response to tumour invasion. The expression of cytokeratins, hyperkeratosis, inflammatory infiltration and amyloid deposition are useful findings indicating the "stage" in Bowen disease.

Cytokeratin (CK5, CK8, CK14) expression and presence of progenitor stem cells in human fetal thymuses.

The aim of the current study was to observe the expression of cytokeratins in human fetal thymuses. Specific cytokeratin markers in adult humans and mice have been well described but there has been little similar work on human fetuses. We also aimed to see whether progenitor stem cells that could be harvested to treat various immunodeficiency disorders are present in fetal thymic tissue. Thymuses obtained from 30 aborted human fetuses (12 to 31 weeks) were examined immunohistochemically to investigate changes in cytokeratin expression in the epithelial cells (TEC) at various gestational ages. Before 16 weeks of gestation, cortical (cTEC) and medullary (mTEC) TEC exhibited homogenous staining for cytokeratins CK8 and CK5. After 16 weeks there was differential staining, with cTEC positive for CK8 and mTEC for CK5 and CK14. Interestingly, both CK5 + CK8+ progenitor stem cells were present in the fetal thymic cortex at all gestational ages, with a relatively high number from 12 to 16 weeks. Cytokeratin expression in fetal thymuses was quite different from that in the adult thymus owing to the presence of undifferentiated progenitor stem cells in fetal thymic stroma along with differentiated TEC. The best time to harvest these progenitor stem cells from fetal thymic stroma in order to treat various immune deficiency disorders appears to be 12-16 weeks. Clin. Anat. 29:711-717, 2016. © 2016 Wiley Periodicals, Inc.

Intermediate filaments of zebrafish retinal and optic nerve astrocytes and Müller glia: differential distribution of cytokeratin and GFAP

BackgroundOptic nerve regeneration (ONR) following injury is a model for central nervous system regeneration. In zebrafish, ONR is rapid - neurites cross the lesion and enter the optic tectum within 7 days; in mammals regeneration does not take place unless astrocytic reactivity is suppressed. Glial fibrillary acidic protein (GFAP) is used as a marker for retinal and optic nerve astrocytes in both fish and mammals, even though it has long been known that astrocytes of optic nerves in many fish, including zebrafish, express cytokeratins and not GFAP. We used immunofluorescence to localize GFAP and cytokeratin in wild-type zebrafish and transgenic zebrafish expressing green fluorescent protein (GFP) under control of a GFAP promoter to determine the pattern of expression of intermediate filaments in retina and optic nerve.FindingsGFAP labeling and GFAP gene expression as indicated by GFP fluorescence was found only in the Müller glial cells of the retina. Within Müller cells, GFP fluorescence filled the entire cell while GFAP labelling was more restricted in distribution. No GFAP expression was observed in optic nerves. Cytokeratin labeling of astrocytes was observed throughout the optic nerve and less intensely in cells in the retinal inner plexiform layer. The retinal inner limiting membrane was strongly labeled by anti-cytokeratin.ConclusionsStudies of astrocyte function during ONR in zebrafish cannot solely rely on GFAP as an astrocyte marker or indicator of reactivity. Future studies of ONR in zebrafish should include evaluation of changes in cytokeratin expression and localization in the optic nerve.

A new murine model for bronchiolitis obliterans post-bone marrow transplant.

Bronchiolitis obliterans (BO) is a major problem in lung transplantation and is also part of the spectrum of late-onset pulmonary complications that can occur after hematopoietic stem cell transplant. Better mouse models are needed to study the onset of this disease so that therapeutic interventions can be developed. Our goal was to develop a BO mouse model. Recipients were lethally conditioned and given a rescue dose of T-cell-depleted, allogeneic bone marrow (BM) supplemented with a sublethal dose of allogeneic T cells. At 2 months post-BM transplant, the lungs had extensive perivascular and peribronchiolar inflammation consisting of CD4(+) T cells, CD8(+) T cells, B cells, macrophages, neutrophils, and fibroblasts. In contrast to the acute model, histology showed airway obstruction consistent with BO. Epithelial cells of airways in the early stages of occlusion exhibited changes in expression of cytokeratins. Although the lung had severe allogeneic BM transplant-mediated disease, there was only mild to moderate graft-versus-host disease in liver, colon, skin, and spleen. High wet/dry weight ratios and elevated hydroxyproline were seen, consistent with pulmonary edema and fibrosis. Mice with BO exhibited high airway resistance and low compliance. Increases in many inflammatory mediators in the lungs of mice that develop BO were seen early post-transplant and not later at the time of BO. This new mouse model will be useful for the study of BO associated with late post-hematopoietic stem cell transplant onset and chronic graft-versus-host disease, which also leads to poor outcome in the lung transplant setting.

Differentiation of separated mouse mammary luminal epithelial and myoepithelial cells cultured on EHS matrix analyzed by indirect immunofluorescence of cytoskeletal antigens.

We have previously demonstrated that purified virgin mouse mammary luminal epithelial and myoepithelial cells promiscuously express cell type-specific cytokeratins when they are cloned in vitro. Changes in cytokeratin expression may be indicators of the loss or change of the differentiated identity of a cell. To investigate the factors that may be responsible for the maintenance of differentiated cellular identity, specifically cell-cell and cell-matrix interactions, we cloned flow-sorted mouse mammary epithelial cells on the extracellular matrix (ECM) derived from the Engelbreth-Holm-Swarm murine sarcoma (EHS matrix). Changes in cell differentiation on EHS, compared with culture on glass, were analyzed by comparing patterns of cytokeratin expression. The results indicate that ECM is responsible for maintenance of the differentiated identity of basal/myoepithelial cells and prevents the inappropriate expression of luminal antigens seen on glass or plastic. Luminal cell identity in the form of retention of luminal markers and absence of basal/myoepithelial antigens, on the contrary, appears to depend on homotypic cell-cell contacts and interactions. The results also show that luminal cells (or a subpopulation of them) can generate a cell layer that expresses only basal cytokeratin markers (and no luminal cytokeratin markers) and may form a pluripotent compartment. (J Histochem Cytochem 47:1513-1524, 1999)

Tobacco smoke-induced alterations of cytokeratin expression in the rat nasal cavity following chronic inhalation of room-aged sidestream smoke

In a 12-month inhalation study on rats using room-aged sidestream smoke (RASS, 12 μg total particulate matter (TPM)/l) as an experimental surrogate for environmental tobacco smoke (ETS), we investigated differentiation changes, i.e. altered cytokeratin (CK) expression, in the epithelial lining at nasal cavity level 1 (NL1) (anterior portion of nasal cavity), and their correlation with histomorphological changes. In addition to conventional histopathological examination, routine paraffin sections were immunohistologically stained for various rat CK and evaluated. Changes in CK expression were observed in the nonciliated respiratory epithelium of maxilloturbinate, lateral wall, and nasoturbinate: in basal cells, increase of CK14 and CK18 and decrease of CK15; in nonciliated columnar cells, increase of CK15 and CK19. These CK changes had histomorphological correlates, i.e. reserve cell hyperplasia and squamous metaplasia. CK expression changes were also seen at sites without histomorphological changes, e.g. enhanced expression of CK14, CK18 in ciliated cells at the dorsal meatus, and CK15 at the septum. Most of the CK expression changes seen after 1 year of RASS exposure resembled the changes previously seen after 8 days of exposure.

Cytokeratin expression patterns in the rat respiratory tract as markers of epithelial differentiation in inhalation toxicology. II. Changes in cytokeratin expression patterns following 8-day exposure to room-aged cigarette sidestream smoke.

The expression of specific cytokeratin (CK) polypeptide patterns is a sensitive marker of the cytoskeletal differentiation of epithelial cells. We developed an immunohistochemical method to assess CK expression patterns in the rat respiratory tract using serial paraffin-embedded sections from the nasal cavity, trachea, and lung. In the present study, this method was used to detect exposure-related differences in CK expression patterns in adult Wistar rats following inhalation of room-aged sidestream smoke (11 mg total particulate matter/m3 air, 8 days, 12 hr/day, whole body). In the anterior nasal cavity level 1 (NL1), changes in CK expression patterns were observed in the respiratory epithelium of the lateral wall and the maxilloturbinate (CK14, CK15, and CK18) and in the squamous epithelium of the ventral meatus (CK13). At nasal cavity level 2 (NL2), immediately behind NL1, changes were observed in the olfactory epithelium (CK13, CK14, and CK18) and in the respiratory epithelium of the septum (CK7 and CK19), the lateral wall (CK7 and CK13), and the lateral aspect of the maxilloturbinate (CK14). Changes were also observed in the submucosal glands, nasolacrimal duct, and vomeronasal organ. In the trachea only CK7 expression changed, and in the lung expression of CK7 (bronchioli) and CK8 (bronchus) changed; the expression of other CK polypeptides did not change. The observed changes in CK expression at NL1 correlated with the histomorphological changes, whereas CK expression changes were also seen in the olfactory and respiratory epithelia at NL2 and in the trachea and lung, where no histomorphological changes were seen. These findings indicate that changes in CK expression in respiratory tract epithelial cells are a sensitive marker for cellular stress response.

Changes in cytokeratin expression in epidermal keratinocytes during wound healing

In order to investigate the re-epithelialization process during wound healing, the hair on the back of guinea pigs was shaved and then excisional wounds were made through the entire thickness of the skin. Histological changes were observed and changes in the expression of different cytokeratin polypeptides were examined using an immunohistochemical technique. Immunohistochemical study revealed that the proliferating and migrating keratinocytes expressed the same cytokeratins as the basal cells of normal epidermis. In addition, the entire epidermis of fairly remote areas from the edges of the wound where no thickening was observed showed a temporarily abnormal staining pattern. The suprabasal cells in the regenerating epidermis temporarily expressed cytokeratins not only specific for suprabasal cells but also specific for basal cells. The cytokeratins expressed in normal basal keratinocytes were also present in the thickened granular layers. These data indicate that the expression of cytokeratins in the epidermal keratinocytes (even in fairly remote areas from the wound edges) changes during wound healing, that the origin of the migrating keratinocytes from the remaining epidermis seems to be the basal cells in the epidermis, and that the appearance of keratohyalin granules is not related to changes in cytokeratin expression.

Differential expression of cytokeratin mRNA in hamster squamous epithelia as observed by in situ hybridization using human cytokeratin cRNA probes.

In this hybridohistochemical study, we investigated the expression of cytokeratin (CK) mRNA in the keratinizing squamous epithelium of hamster cheek pouch and esophagus, using eight different digoxigenin-labelled RNA probes complementary to human CK mRNAs. CK 4, CK 6, CK 8, CK 14, and CK 15 RNA probe obviously hybridized with hamster counterpart mRNA(s) in the cheek pouch as well as in the esophageal epithelium. However, using the CK 10-specific RNA probe, only the cheek pouch epithelium exhibited a positive reaction. We were not able to detect any positive signal for the CK 18 or for the CK 19 RNA probe. We observed three different CK mRNA distribution patterns in the cheek pouch epithelium, and four in the esophageal epithelium. The differences in expression and distribution pattern of CK mRNAs between the two types of epithelia suggest that the hamster CK polypeptide family comprises at least six different species. We also conclude that human cRNA probes for CK mRNAs may provide a way to detect changes in CK expression and distribution during induced non-neoplastic and neoplastic changes in the hamster cheek pouch model. This may also help to elucidate the molecular pathogenesis of squamous-cell carcinoma.

Expression of cytokeratin-mRNAs in squamous-cell carcinoma and balloon-cell formation of human oesophageal epithelium

Using digoxigenin-labelled cRNA probes, relationships between morphological characteristics and in situ hybridization for cytokeratin (CK)-mRNAs were analysed in cases of squamous-cell carcinoma of variable differentiation and in balloon-cell formation within the oesophageal mucosa. The present results were correlated to our previous findings on normal oesophageal epithelium. Our results from in situ hybridization study on oesophageal squamous-cell carcinoma provide strong evidence that changes in CK expression occur with differences in malignant potential. Cells of poorly differentiated carcinoma lose an ability to produce CK-mRNAs characteristic of their normal progenitor cells. Moderately differentiated and, still more pronounced, well differentiated carcinoma cells retain an ability to produce CKs characteristic of their tissue of origin (CK 6, CK 14, CK 15 and CK 19). Furthermore, well differentiated carcinoma cells may also gain an ability to synthesize new types of CKs that are not characteristic of the normal oesophageal epithelium (CK 8 and CK 18 characteristic of most simple epithelia, and CK 10 characteristic of keratinizing epithelia). Moreover, some oesophageal CK-genes are expressed in an obviously higher amount (CK 6, CK 14, and CK 19), but the expression of genes coding for the oesophageal differentiation-related CKs (CK 4 and CK 13) is obviously decreased or apparently lost. At the interface zone, observed in sections of well differentiated carcinomas, CK 8 and CK 18 mRNA were expressed in intermediate cell layers, and the centrally located cell layers were found positive for CK 10 mRNA. These findings largely extend the existing results from immunoblotting and immunohistochemical studies. The reduced or non-detectable expression of oesophageal differentiation-related CK-mRNAs (CK 4 and CK 13) on the appearance of balloon cells, suggests molecular changes that may be a marker for pathological progression. In addition, the abundant expression of CK 6 and CK 14 mRNA within areas of balloon-cell formation showing basal hyperplasia, and the higher expression of CK 19 in comparison with normal epithelium, points rather to de-differentiation than to normal vertical differentiation of the oesophageal epithelium. Whether CK-mRNAs can be used as biomarkers for evaluation of oesophageal pathologies remains to be further elucidated.

Intermediate filament proteins and epithelial differentiation in the embryonic ovary of the rat

Abstract The development and sexual differentiation of gonads in female rat embryos and fetuses between the ages of 11 and 17 days was studied by immunocytochemical analysis of intermediate filament proteins and laminin by light and electron microscopy. In the 11-day-old pregonadal embryo, the surface epithelial cells in the ventral cortex of the mesonephros contained desmin but not cytokeratin or vimentin. The development of the gonad began on the following day by proliferative growth of the mesonephric surface cells, which like the subepithelial cells soon expressed vimentin in addition to desmin. The differentiation continued by formation of separate epithelial cell clusters, which joined into cords, irregular in shape and size. Desmin disappeared from the cord cells and cytokeratins appeared while vimentin remained in all somatic cell types. Desmin was especially abundant in some stromal cells adjacent to the epithelial tissues. After the segration of the basic ovarian tissues, vimentin and desmin decreased and cytokeratins appeared in the surface epithelial cells. New changes in cytokeratin expression appeared with the differentiation of the embryonic cords in a sex-specific manner with gradual decrease of reactivity for cytokeratin 18. No immunoreaction to the neurofilament proteins was found at the present ages, and the germ cells were negative for intermediate filaments. The results show that desmin is expressed in several primitive ovarian and mesonephric cells even though they are not myogenic. The sexual differences emerge after the incipient formation of the genetically female gonad, as different organization of the internal epithelial tissue with different timing of changes in intermediate filament proteins when compared with the male gonad.

Changes in cytokeratin expression during the development of the human oral mucosa

The changes in cytokeratin expression by the developing oral mucosa of 10 to 23-week-old human fetuses were studied by indirect immunofluorescence using a panel of 15 monoclonal antibodies. The lining and masticatory mucosae were incompletely differentiated in 10-wk fetuses, since they expressed identical patterns of cytokeratins (CK 4, 5, 8, 13, 18, 19 and probably CK 14, 16, 17) very similar to that of adult alveolar mucosa. The main difference was the presence of cytokeratins 8, 18 and 19 in embryonic tissues. Cytokeratins 1, 2, 10 and 11 began to appear in gingival and hard palate epithelium from wk 11, predicting the differentiation of the masticatory mucosa by wk 16. The patterns of cytokeratin expression in the 23-wk fetus in the lining and masticatory mucosae appear to be different. In lining mucosa, the only difference from the 10th wk is a decrease in cytokeratins 8, 18 and 19, whereas the pattern of cytokeratin expression in masticatory mucosa (CK 1, 2, 4, 5, 8, 10, 11, 13, 18, 19 and probably CK 14, 16 and 17) is now very near that of adult gingiva. This pattern appears, as in the adult, to be similar to that of the epidermis in the same period.

Alterations in cytokeratin expression precede histological changes in epithelia of vitamin A-deficient rats.

Normal epithelial cell differentiation is characterized by the production of distinct cytokeratin proteins. It is well known that epithelia of several organs show squamous metaplasia in a vitamin A-deficient status. It is not yet known whether these histological changes are concomitant with a change in cytokeratin expression. Therefore, 3-week-old female rats (BN/BiRij) were fed a vitamin A-deficient diet for 8 weeks. The cytokeratin expression in epithelia of various organs was monitored immunohistochemically during the induction of vitamin A deficiency. Therefore, monoclonal antibodies specific for human cytokeratin 4, 5, 5 + 8, 7, 10, 14, 18 and 19 were used. In a normal vitamin A status, the distributional pattern for the different cytokeratins in rats was similar to that reported for human tissue. No change in cytokeratin expression was seen in trachea, skin, liver and colon at any time point studied. Squamous metaplasia in urinary bladder and salivary glands was observed after six weeks on the vitamin A-deficient diet. This was concomitant with a substitution of cytokeratins 4, 5 + 8, 7, 18 and 19 by cytokeratin 10. The latter cytokeratin is specific for keratinized squamous epithelium. A change in cytokeratin expression was observed in bladder, ureter, kidney, salivary glands, uterus and conjunctiva before histological alterations appeared. In conclusion, the changes in cytokeratin expression observed under vitamin A deficiency in epithelia in vivo are in agreement with those described in other studies for epithelial cells in vitro. The changes in cytokeratin expression and the subsequent differentiation into squamous cells occurs in basal cells of the bladder but not in transitional cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in cytokeratin expression accompany squamous metaplasia of the human respiratory epithelium.

To determine the characteristics of metaplastic changes of the nasal respiratory epithelium, the distribution of individual cytokeratins (CKs) was studied immunohistochemically and by two-dimensional gel electrophoresis. The authors define four types of changes of the normal pseudostratified columnar epithelium: (1) transitional pseudostratified epithelium (first unusual CK.: no. 13); (2) stratified columnar epithelium (increased expression of CKs 4 and 13; CKs 7, 8, 18 and 19 reduced); (3) stratified squamous epithelium, nonkeratinized (appearance of CK 16); and (4) stratified squamous epithelium, keratinized (expression of CKs 1 and 10, variable CK5 and 14 patterns in basal cells). These phenotypes were found simultaneously within single specimens, resulting in apparent overall variability in the immunohistochemical staining patterns. Spatially, changes in CK expression towards "normal" parts were not abrupt but rather gradual. Biochemical data confirmed the immunohistochemical findings and added CK 6 to the pattern of altered nasal mucosa. The findings of this study suggest a stem cell metaplasia in the nasal epithelium which is based on its inherent bimodal developmental programme. A gradual loss of normal respiratory epithelial differentiation, as seen by the loss of CKs 7, 8, and 18, was paralleled by the appearance of squamous epithelial type CKs, e.g. the expression of CKs 1, 10 and 13. Basal cell types CKs 5, 14, 17 and 19 were maintained during this process. Implications of these results for general concepts of CK expression in the metaplastic process are discussed.

Correlation of DNA Ploidy Levels with Altered Cytokeratin Patterns in Rat Bladder Tumors

Flow cytometry analysis of primary bladder carcinoma cells is appropriate for demonstrating the association between the presence of aneuploid cells and increased malignant potential for transitional cell carcinoma (TCC). Our laboratory previously has reported a specific alteration in the cytokeratin (CK) pattern of experimentally induced bladder carcinomas in rats. Unique immunohistochemically detectable changes in CK expression were the loss of CK 13 expression in invasive TCC cells and the loss of CK 19 expression in induced TCC. We now report the correlation of these changes in CK expression with cellular aneuploidy of the induced bladder carcinomas. Bladder carcinomas were induced in rats by direct instillation of N-methyl-N-nitrosourea. Immunohistochemistry was performed on the induced tumors using four commercially available monoclonal antibodies specific for CK 18 (TR1031), CK 13 (K8.12), CK 19 (K4.62), and the CKs 5, 7, and 8 (K8.13). Flow cytometry data from the induced bladder carcinomas was analyzed and the DNA index, proliferative index, and percent aneuploid cells were calculated for each time point. The percent aneuploid cells and CK 19 staining were tested statistically and were shown to be negatively correlated. We therefore hypothesize that the combination of the loss of CK 19 as detected by the antibody K4.62 coupled with the presence of aneuploid cells in histopathologically diagnosed invasive TCC is a significant factor in predicting the prognosis for any given diagnosis.

Demonstration of Changes in Cytokeratin Expression in Condylomata Accuminata in Relation to the Presence of Human Papilloma Virus as Shown by a Combination of Immunohistochemistry and In Situ Hybridization

Human papillomavirus (HPV) can be detected in, and is probably involved in the etiology of, the majority of anogenital neoplasias. Infection with the virus induces a number of events in the infected epithelial cells that may lead to the development of benign or malignant tumors. One change that can be detected in the infected cells is in squamous differentiation, which is reflected by the pattern of cytokeratin polypeptide expression. By studying this pattern in relation to the presence of the virus, an indication may be obtained of the influence of the virus on the cellular differentiation in individual cells. By using a combination of DNA in situ hybridization and immunohistochemistry, for HPV and cytokeratin polypeptides, respectively, we studied the presence of HPV6 or HPV11 in condylomata accuminata derived from anogenital skin in relation to the cytokeratin polypeptides K1, 4, 8, 10, 14, and 18. We found that in many samples the presence of the skin-type cytokeratins K1 and K10 was decreased, whereas K13, and to a lesser degree K4, appeared. The cellular localization of these aberrations in cytokeratin expression could be related to the presence of HPV6 or 11 DNA in the tissue.

Changes in cytokeratin expression in gingiva during inflammation

Cytokeratins represent specific markers of certain pathways of epithelial differentiation. The purpose of this study was to describe the alterations of cytokeratin pattern and topographical distribution of individual cytokeratins in inflamed gingiva. Five healthy and 15 inflammatory samples of human gingiva were studied. From each biopsy, cryostat sections allowed histological staining, immunofluorescence microscopy using a battery of monoclonal antibodies to cytokeratins, and gel electrophoresis. The results show marked differences in cytokeratin expression by healthy epithelia as compared with inflamed gingiva: in suprabasal cell layers there were reductions or disappearance of cytokeratins 1, 2 and 10, 11--specific for terminal differentiation--and increased expression of cytokeratins 4 and 13, as well as--in basal and parabasal cell layers--expression of cytokeratin 19. These alterations might represent an adaptation of involved epithelia to the alterations brought about by the inflammatory process.

Extensive changes in cytokeratin expression patterns in pathologically affected human gingiva

The stratified squamous epithelium of the oral gingiva and the hard palate is characterized by a tissue architecture and a cytoskeletal composition similar to, although not identical with, that of the epidermis and fundamentally different from that of the adjacent non-masticatory oral mucosa. Using immunocytochemistry with antibodies specific for individual cytokeratins, in situ hybridization and Northern blots of RNA with riboprobes specific for individual cytokeratin mRNAs, and gel electrophoresis of cytoskeletal proteins of microdissected biopsy tissue samples, we show changes in the pattern of expression of cytokeratins and their corresponding mRNAs in pathologically altered oral gingiva. Besides a frequently, although not consistently, observed increase in the number of cells producing cytokeratins 4 and 13 (which are normally found as abundant components in the sulcular epithelium and the alveolar mucosa but not in the oral gingiva) and a reduction in the number of cells producing cytokeratins 1, 10 and 11, the most extensive change was noted for cytokeratin 19, a frequent cytokeratin in diverse one-layered and complex epithelia. While in normal oral gingiva cytokeratin 19 is restricted to certain, sparsely scattered cells of --or near--the basal cell layer, probably neuroendocrine (Merkel) cells, in altered tissue of inflamed samples it can appear in larger regions of the basal cell layer(s) and, in apparently more advanced stages, also in a variable number of suprabasal cells. Specifically, our in situ hybridization experiments show that this altered suprabasal cytokeratin 19 expression is more extended at the mRNA than at the protein level, indicating that cytokeratin 19 mRNA synthesis may be a relatively early event during the alteration. These changes in cytokeratin expression under an external pathological influence are discussed in relation to other factors known to contribute to the expression of certain cytokeratins and with respect to changes occurring during dysplasia and malignant transformation of oral epithelia.