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At least 19 recordsLinked to original sources
PubMed1979

[Tactile cells (Merkel cells) during degeneration of cat sinuous hairs].

Degeneration of the tactile cells in epithelium of the cat sinuous hairs after sectioning the infraorbital nerve manifests itself as cytoplasmic vacuolization and induration with electron opaque bodies in it, changes in nuclear configuration and in chromatin density. At all stages of the experiment the tactile cells were practically observed demonstrating various degenerative signs. On the 45th day after sectioning the tactile cells disappeared completely. Structural changes in the tactile cells were preceded by degeneration and complete disappearance of tactile menisci from epithelium of the sinuous hairs. Perhaps, sensitive innervation is necessary to maintain differential status of the tactile cells in epithelium.

Animals↗
PubMed2002

Proneural and proneuroendocrine transcription factor expression in cutaneous mechanoreceptor (Merkel) cells and Merkel cell carcinoma.

Merkel cells form part of the peripheral neuroendocrine system of the skin and act as mechanoreceptors in touch response. Merkel cell carcinoma (MCC) is a rare, aggressive disease with similarities to small cell lung cancer (SCLC), which is also of neuroendocrine origin. We previously identified a novel DNA binding protein complex specific for MCC suspension cell lines, termed Merkel nuclear factor (MNF) by its binding to the POU-IV family DNA binding consensus sequence. Here we report that MNF contains the POU-IV family member Brn-3c and that Brn-3c is expressed in normal Merkel cells. Additionally, Brn-3c protein reactivity is restricted to a subset of MCC biopsies and is not seen in biopsies revealing adherent, variant cell lines lacking neuroendocrine markers. Recently, proper development of murine Merkel cells was shown to require the proneural basic helix-loop-helix transcription factor, atonal family member, MATH1. We demonstrate a correlation between Brn-3c and HATH1 reactivity in MCC biopsies and cell lines with retention of neuroendocrine phenotype. In SCLC, the related basic helix-loop-helix transcription factor HASH1 is responsible for neuroendocrine phenotype, but HASH1 transcripts were not detected in MCC cell lines. We propose that HATH1 and Brn-3c may form a transcriptional hierarchy responsible for determining neuroendocrine phenotype in Merkel cells and that lack of Brn-3c and/or HATH1 in MCC may indicate a more aggressive disease requiring closer patient follow-up.

Basic Helix-Loop-Helix Proteins↗
PubMed2003

MOC-31/Ep-CAM immunoreactivity in Merkel cells and Merkel cell carcinomas.

AIMS: To evaluate the monoclonal antibody MOC-31 in Merkel cell carcinomas and normal Merkel cells. Merkel cell carcinoma is a rare and aggressive tumour that occurs mainly in elderly individuals. The histological diagnosis of Merkel cell carcinoma can be difficult because it looks similar to other small blue cell tumours, particularly skin metastases of small-cell lung carcinomas. This antibody recognizes the epithelial cell adhesion molecule (Ep-CAM), that has been assigned to the small cell lung cancer cluster 2 of antibodies. To the best of our knowledge, immunostaining for MOC-31/Ep-CAM has not been previously described in Merkel cells or Merkel cell carcinomas. METHODS AND RESULTS: Thirty-one cases of Merkel cell carcinoma and three samples of normal human fingertip were selected to analyse the expression of MOC-31/Ep-CAM by immunohistochemistry. A high number of Merkel cell carcinomas (21/31, 67.7%) showed intense and readily interpretable positivity. Immunostaining was diffuse or focal and always localized to the plasma membrane. Normal Merkel cells of human fingertip also showed plasma membrane immunoreactivity for MOC-31/Ep-CAM. CONCLUSION: The demonstration of positivity for MOC-31/Ep-CAM in Merkel cell carcinomas precludes the use of this immunohistochemical marker to distinguish between tumours and skin metastases of small-cell lung carcinoma.

Adult↗
PubMed1996

Differences of bcl-2 protein expression between Merkel cells and Merkel cell carcinomas.

The bcl-2 gene, originally identified in B-cell lymphomas, encodes for proteins which may assume oncogenic functions by blocking apoptosis. Bcl-2 proteins are broadly distributed among various tissues, including epithelial ones. Within the skin, bcl-2 is strongly expressed in melanocytes, but its further distribution is yet unclear. The Merkel cells, neuroendocrine-epithelial cells of the skin, are present within the epidermis and hair follicles, mostly nerve-associated, and are believed to be postmitotic and long lived. Possibly they give rise to the malignant Merkel cell carcinomas. In the present study we investigated the bcl-2 expression on the protein level by means of immunohistochemical techniques including double confocal laser scanning microscopy, as well as on the RNA level by RT-PCR techniques, in Merkel cells, Merkel cell carcinomas, and cell lines. Merkel cells were identified by double staining for cytokeratins 20 or 8/18. We demonstrate that fetal epidermal and dermal Merkel cells are immunostained for bcl-2 protein, most of them clearly weaker than melanocytes. Adult Merkel cells also express bcl-2 protein very heterogeneously, mostly weak. In contrast, Merkel cell carcinomas are usually strongly positive for bcl-2 protein with some degree of heterogeneity. This is different from malignant melanomas in which bcl-2 expression is reduced as compared to normal melanocytes. Bcl-2 gene expression was also shown for Merkel cell carcinoma cell lines on both the mRNA and the protein level. Possibly bcl-2 protein expression is downregulated during the life span of Merkel cells, arguing that they may succumb to a certain cell turnover. The comparably high bcl-2 protein level in Merkel cell carcinomas may reflect peculiar biological and clinical characteristics.

Adult↗
PubMed1996

Merkel cells and Merkel cell carcinoma express the BCL-2 proto-oncogene.

The bcl-2 proto-oncogene, which is involved in the regulation of apoptosis, is expressed in a wide variety of fetal and adult tissues. We and others have demonstrated recently that in the human skin melanocytes, nervus cells and melanoma cells express bcl-2 constitutively. In the present study, we have analysed the expression of bcl-2 in Merkel cells and in Merkel cell carcinomas. In 2 colour immunofluorescence staining, normal human Merkel cells as identified by the expression of cytokeratins 8, 18 and 20, were also anti-bcl-2 positive. Staining of paraffin sections of Merkel cell carcinomas with an anti-bcl-2 monoclonal antibody revealed strong bcl-2 protein immunoreactivity in all 5 tumors tested. Serial sections of Merkel cell carcinomas stained with the monoclonal antibodies CK 20, CAM 5.2, anti-neuron-specific enolase and anti-bcl-2 showed that the anti-bcl-2 reactive cells were indeed tumor cells. Our data demonstrate for the first time, that normal human Merkel cells and Merkel cell carcinomas express bcl-2 constitutively. Considering the biological function of the bcl-2 proto-oncogene, i.e., its anti-apoptotic effect, it is conceivable that in the near future, modulations of the expression of this protein may offer a new strategy in the therapy of bcl-2 expressing tumors such as Merkel cell carcinoma.

Adult↗
PubMed1996

Merkel cells and Merkel cell carcinoma express the BCL-2 proto-oncogene.

The bel-2 proto-oncogene, which is involved in the regulation of apoptosis, is expressed in a wide variety of fetal and adult tissues. We and others have demonstrated recently that in the human skin melanocytes, nevus cells and melanoma cells express bcl-2 constitutively. In the present study, we have analysed the expression of bcl-2 in Merkel cells and in Merkel cell carcinomas. In 2 colour immunofluorescence staining, normal human Merkel cells as identified by the expression of cytokeratins 8, 18 and 20, were also anti-bcl-2 positive. Staining of paraffin sections of Merkel cell carcinomas with an anti-bcl-2 monoclonal antibody revealed strong bcl-2 protein immunoreactivity in all 5 tumors tested. Serial sections of Merkel cell carcinomas stained with the monoclonal antibodies CK 20, CAM 5.2, anti-neuron-specific enolase and anti-bcl-2 showed that the anti-bcl-2 reactive cells were indeed tumor cells. Our data demonstrate for the first time, that normal human Merkel cells and Merkel cel carcinomas express bcl-2 constitutively. Considering the biological function of the bcl-2 proto-oncogene, i.e., its anti-apoptotic effect, it is conceivable that in the near future, modulations of the expression of this protein may offer a new strategy in the therapy of bcl-2 expressing tumors such as Merkel cell carcinoma.

Adult↗
PubMed1983

Merkel cells and Merkel cell tumors. Ultrastructure, immunocytochemistry and review of the literature.

Certain monomorphic cellular tumors that occur in the dermis have been called trabecular carcinomas or Merkel cell tumors. Forty-six cases have been reported to date and the literature on these is reviewed here, with six additional cases reported. Cytologic features include sparse cytoplasm, dispersed chromatin with inconspicuous nucleoli in round nuclei and many mitoses. Trabeculae and pseudorosettes may be identified. Electron microscopy is required for definitive diagnosis. Like normal Merkel cells, tumor cells contain electron-dense granules (80-200 nm), 10 mm filaments and desmosomes. Filament-rich cytoplasmic spikes were found in four tumors. These resemble corresponding protrusions of normal Merkel cells and have not been described in other APUDomas.

Adenocarcinoma↗
PubMed1984

Contribution to ontogenesis of Merkel cells.

Merkel cells appear in the epidermis of planum nasale of the rat fetuses from the 16th day of i. u. development, namely in the 2nd-3rd layer of epidermal cells. Nerve fibres appear in the subepidermal connective tissue from the 20th day of i.u. development. Long cytoplasmic processes filled in with specific dense core vesicles grow from Merkel cells against them. Intraepidermally, nerve fibres appear in postnatal period (from 3rd day after birth). Granular vesicles of Merkel cells probably have the leading role in the formation and maintenance of contacts between Merkel cell and the nerve ending. The results of studying ontogenetic development of Merkel cells in the rat are favour of hypothesis about the differentiation of Merkel cells in the epidermis, however, the possibility of secondary equipment of epidermis with Merkel cells independently on the development of nerve fibres is not eliminated.

Animals↗
PubMed2001

Telomerase activity of Merkel cell carcinomas and Merkel cell carcinoma-derived cell cultures.

Merkel cell carcinomas are rare malignant tumors of the skin, which are predominantly observed in elderly patients (mean age 65-70 years). It is believed but not yet proven that these tumors are derived from the Merkel cells of the epidermis and hair follicles. The Merkel cells themselves probably originate from an asymmetric cell division of basal keratinocytes and the resulting differentiated Merkel cells have presumably, at least in humans, lost their growth potential. The capability of indefinite cell division in germ line cells and in the great majority of malignant tumors as well as an increased growth potential in certain somatic cells (such as basal cells of renewable tissues) is correlated with cellular telomerase activity, which is absent in differentiated somatic cells. In this study the telomerase activity in cryostat sections of frozen Merkel cell tumor biopsies and in in vitro cultivated Merkel cell carcinoma cells was analyzed. We detected telomerase activity in four tumors and three of four cell cultures. These results show that despite their pronounced neuroendocrine differentiation and their occurrence in patients of advanced age, Merkel cell carcinomas possess telomerase activity similar to that of common carcinoma types.

Aged↗
PubMedDate not supplied

An immunocytochemical study of the carbonic anhydrase I isoenzyme in human oral Merkel cells.

Merkel cells in human buccal mucosa and hard palate possess the carbonic anhydrase I isoenzyme (CAI). CAI colocalized immunocytochemically with a range of Merkel cell cytokeratins, namely CK 7, 8, 18, 19 and 20. No other cells in the oral epithelium were immunoreactive for the CAI antibody. The presence of the enzyme may be related to the function of sensory receptors that produce a sustained response to a maintained mechanical stimulus.

Adult↗
PubMed1999

Intraepidermal cytokeratin 7 expression is not restricted to Paget cells but is also seen in Toker cells and Merkel cells.

Histologically, extramammary Paget's disease and mammary Paget's disease (MPD) are characterized by large atypical cells distributed throughout the epidermis. Although classic examples of these disorders are easily diagnosed on morphologic grounds, some cases may cause differential diagnostic problems. Immunohistology with a wide variety of antibodies has been used as an aid for the identification of Paget cells, for their distinction from other entities, and for investigation of the origin or nature of the disorder. Recently, cytokeratin 7 has been proposed as a specific and 100% sensitive marker for Paget's disease. We studied 22 cases of mammary Paget's disease and 22 cases of extramammary Paget's disease with and without an underlying malignancy for their reactivity with monoclonal antibodies to cytokeratin 7 (CK7) and cytokeratin 20 (CK20). Our studies show that anti-CK7 is an effective but not 100% sensitive marker for Paget cells, staining 21 of 22 cases of mammary Paget's disease and 19 of 22 cases of extramammary Paget's disease, whereas CK20 stained 0 of 17 cases of mammary Paget's disease and 6 of 19 cases of extramammary Paget's disease. We also demonstrate that CK7, but not CK20, highlights intraepidermal clear cells with bland nuclear features (Toker cells) that have been reported in 11% of normal nipples. By using CK7 as a marker, however, we were able to identify Toker cells in most of the nipples we studied: 8 of 15 nipples from mastectomy patients without Paget's disease, and 15 of 18 autopsy cases (both male and female) with normal breasts and nipples. It also permitted us to perform more extensive phenotyping on them, showing that Toker cells share similar antigens with Paget cells and with cells lining the underlying normal lactiferous ducts. In 7 of 15 cases containing CK20-positive Merkel cells, CK7 was also seen to stain Merkel cells. In infrequent cases, Toker cells or Merkel cells may be so numerous focally that a CK7 stain may raise the possibility of involvement of the nipple by Paget's disease. An awareness of the CK7 reactivity of Toker cells and Merkel cells as well as attention to the cytologic features of the case should avoid this problem.

Aged↗
PubMed1995

Neural cell adhesion molecule immunoreactivity in Merkel cells and Merkel cell tumours.

We have analysed the expression of the neural cell adhesion molecule (NCAM) in normal Merkel cells of pig and human skin, and in nine neuroendocrine carcinomas of the skin (Merkel cell carcinomas). NCAM immunoreactivity was observed in virtually all Merkel cells, both in epidermis and vibrissae of pig snout skin and in human epidermis. Immunostaining surrounded the entire surface of Merkel cells and was not restricted to the contact areas between Merkel cells and nerve terminals. All Merkel cell carcinomas studied were also positive for NCAM. The immunostaining pattern of the tumour cells was similar to that observed in normal Merkel cells; the immunoreactivity was confined to the cell membranes. These results suggest that NCAM may be used as an immunohistochemical marker for both Merkel cells and Merkel cell tumours.

Animals↗
PubMed1997

Insights into the Merkel cell phenotype from Merkel cell carcinoma cell lines.

Merkel cell carcinoma (MCC) of the skin is an aggressive form of skin cancer and is being seen with increasing incidence in Queensland. We have recently established a number of MCC cell lines and characterized these for growth, morphology, expression of neuroendocrine markers and radiation sensitivity. As a result, cell lines were grouped into four classes by their morphology in a similar way to small cell lung cancer (SCLC) cell lines. Types I and II cell lines grew slowly as tight spherical clusters suspended in the medium, with Type II cell lines less densely packed than the Type I cell lines. Type III cell lines grew as flat 2-dimensional clusters and had shorter doubling times and Type IV cell lines grew as adherent monolayers and had the shortest doubling times. Expression of neuroendocrine markers distinguished those with a classic phenotype from those with a variant one. Mainly morphological Types I and II retained the classic phenotype while Classes III and IV had a variant phenotype. The range of surviving fraction at 2 Gray (SF2 0.2-0.45) seen in MCC cell lines was not as high as seen in SCLC cell lines but the variant ones tended to be more radiation resistant. Examination of POU proteins showed that neuroendocrine phenotype was linked with expression of brn-2, and growth in suspension with brn-3c.

Base Sequence↗
PubMed2002

Primary undifferentiated small cell carcinoma (Merkel cell carcinoma) in a patient after heart transplantation--case report.

Here we report a case of a 48-year-old man after heart transplantation in whom two years after the procedure an appendage germ tumour was diagnosed and a year after its removal in the same area a primary undifferentiated small cell carcinoma (Merkel cell carcinoma) with metastases to the axillary lymph nodes was detected. The diagnosis of Merkel cell carcinoma was confirmed by immunohistochemical staining showing a typical perinuclear expression of cytokeratin 20 with the absence of reactivity with wide spectrum cytokeratin and the presence of neuroendocrine markers of neurone-specific enolase and chromogranin. Primary undifferentiated small cell carcinoma occurs more frequently in patients receiving immunosuppressive treatment as compared with a general population and occurs much more frequently in those below 50 years of age.

Carcinoma, Merkel Cell↗
PubMed1996

The Merkel cell as a possible mechanoreceptor cell.

Merkel cells (MCs) are abundant at the basal layer of various skin in vertebrates, and make synaptic contacts with nerve endings to form the Merkel cell-neurite complex (MCN-complex). It has been established that the MCN-complex is involved in slowly adapting mechanoreception, cutaneous afferents of which are called SAI units in mammals or Ft-I units in frogs. However, the MC function has been the focus of attention, and some hypotheses propose that the site of mechanoreception is at the nerve terminals but not at the MC. In the present review, the possibility that MCs are the mechanoreceptors was focused on recent findings. Irradiation of quinacrine-loaded MCs in the rat hairy skin using excitation light degenerates the MCs selectively with the nerve terminals left intact. Correspondingly, SAI units decrease tonic discharges rapidly, but phasic responses remain intact. Blocking synaptic transmission in the MCN-complexes by divalent or alkyl Ca antagonists in mammals or frogs heavily decreases the tonic mechanical responses of the afferent units, but the phasic responses are rather resistant. Application of anodal current on the Ft-I receptive spots produces tonic discharges as in hair cells or taste cells, while the threshold to elicit the first spike is lower with cathodal than anodal stimulation, in contrast with other secondary sensory cells. These findings indicate that MCs are mechanoreceptors to yield tonic responses, while the nerve terminals may transduce the transient phase. Further studies, particularly on mechanically-gated ionic channels in the MC membrane and on transmitters between the MCs and nerve terminal, are necessary to establish the MC as mechanoreceptors.

Animals↗
PubMed2000

Regressing Merkel cell carcinoma-a case showing replacement of tumour cells by foamy cells.

Merkel cell carcinoma (MCC) is a malignant neuroendocrine tumour with a high rate of recurrence and metastasis. However, some cases of spontaneous regression have recently been reported. We describe the clinical course of an 80-year-old Japanese woman with regressing MCC. We also report histological findings of the regressing tumour for the first time. After the patient's first visit to our hospital, the lesion was a rapidly progressive tumour, but suddenly began decreasing in size, and rapidly regressed. The surface of the tumour flattened, the colour changed from red to dark red, and finally the lesion appeared as a small yellowish plaque. Histopathological analysis of the completely regressed tumour revealed that the tumour cells were completely replaced by numerous foamy cells. This is the first report demonstrating the histopathological features of regressing MCC.

Aged↗
PubMedDate not supplied

Ultrastructural study of taste buds at rest and after stimulation, and comparative study between type III cell and Merkel cells.

Changes in the pore region of the cell membrane have been studied in order to learn if this region plays an active part in the preneural phase of taste. We have observed, though not consistently, that the pore size is variable and that their contents are not constantly amorphous or homogeneous. The results are not so significant, however, as to allow of the formulation of any firm conclusions. The similarity between type III cells and Merkel cells (cells of the tactile system) was surprising. The probable role of the type III cell in taste is discussed.

Animals↗