Merkel cell and Merkel cell-neurite complexes in the gingival and alveolar mucosa of the newborn kittens.
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Animals↗
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Cytomorphology of primary small-cell (Merkel-cell) carcinoma of the skin in fine needle aspirates.
The histologic appearance of primary small-cell carcinoma of the skin (the so-called Merkel-cell tumor) is similar to other small-cell tumors that may metastasize to the dermis. Significance has been placed on the electron microscopic appearance of this tumor since the ultrastructural features of this neoplasm are helpful in distinguishing it from most of the other neoplasms considered in the differential diagnosis. To determine whether any additional morphologic criteria might exist to distinguish this neoplasm, the fine needle aspirate appearance of a primary small-cell carcinoma of the skin was studied and compared to that of similar preparations of other small-cell tumors that could potentially involve the dermis. Cells of this unusual tumor were round and showed neither cohesiveness nor nuclear molding. Mitoses were numerous. The chromatin pattern was bland. The cytologic features of this tumor can aid in the distinction of primary small-cell carcinoma of the skin from other metastatic small-cell neoplastic lesions in the dermis of adults.
Aged↗
Effects of electromagnetic radiation from a cellular telephone on epidermal Merkel cells.
The number of reports on the effects induced by electromagnetic radiation (EMR) from cellular telephones in various cellular systems is still increasing. Until now, no satisfactory mechanism has been proposed to explain the biological effects of this radiation except a role suggested for mast cells. Merkel cells may also play a role in the mechanisms of biological effects of EMR. This study was undertaken to investigate the influence of EMR from a cellular telephone (900 MHz) on Merkel cells in rats. A group of rats was exposed to a cellular telephone in speech position for 30 min. Another group of rats was sham-exposed under the same environmental conditions for 30 min. Exposure led to significantly higher exocytotic activity in Merkel cells compared with the sham exposure group. This finding may indicate the possible role of Merkel cells in the pathophysiology of the effects of EMR.
Animals↗
Immunostaining for thyroid transcription factor 1 and cytokeratin 20 aids the distinction of small cell carcinoma from Merkel cell carcinoma, but not pulmonary from extrapulmonary small cell carcinomas.
OBJECTIVE: To study the expression of thyroid transcription factor 1 (TTF-1) and cytokeratin 20 (CK20) in pulmonary small cell carcinomas, extrapulmonary small cell carcinomas, and Merkel cell carcinomas, and thereby determine whether these markers are helpful in distinguishing these 3 groups of small cell neuroendocrine carcinomas. MATERIALS AND METHODS: Immunostaining for TTF-1 and CK20 was performed in 102 cases of small cell carcinoma (pulmonary, 52; extrapulmonary, 50) and 23 cases of Merkel cell carcinoma. The results for the 3 groups were compared. RESULTS: Thyroid transcription factor 1 was expressed in 82.7% of pulmonary small cell carcinomas, 42.0% of extrapulmonary small cell carcinomas (range, 33.3--53.3% for the various sites), and 0% of Merkel cell carcinomas. Cytokeratin 20 staining was consistently negative in pulmonary small cell carcinomas, and positive in 4.0% of extrapulmonary small cell carcinomas and 100% of Merkel cell carcinomas. CONCLUSIONS: Immunostaining for TTF-1, especially when combined with immunostaining for CK20, can aid in the distinction between Merkel cell carcinoma and small cell carcinoma (both pulmonary and extrapulmonary). However, in individual cases, these markers cannot be used to distinguish between pulmonary and extrapulmonary small cell carcinomas due to the extensive overlap in immunophenotypes.
Carcinoma, Merkel Cell↗
Somatostatin immunoreactive cells and Merkel cells in psoriasis.
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Dendritic Cells↗
A case of intraepidermal Merkel cell carcinoma within squamous cell carcinoma in-situ: Merkel cell carcinoma in-situ?
We report a case of a 79-year-old Caucasian male who presented with a wrist lesion of combined intraepidermal Merkel cell carcinoma and squamous cell carcinoma in-situ. The two tumors were tightly admixed and distinct, and both were without any dermal or invasive components. No features of transition between the two tumors were seen. We suggest the term Merkel cell carcinoma in situ for tumors that demonstrate exclusive intraepidermal proliferation of neuroendocrine cells.
Biomarkers, Tumor↗
Non-innervated Merkel cells and Merkel-neurite complexes in human oral mucosa revealed using antiserum to protein gene product 9.5.
Merkel cells are non-keratinized cells present in many different epithelia, but whose origin and functional role are still controversial. They were here investigated by means of antisera to the neural and neuroendocrine markers protein gene product 9.5 (PGP 9.5), and neurone-specific enolase. The expression of both markers in Merkel cells of human gingival and palatal mucosa was confirmed. Merkel cell-neurite complexes and isolated non-innervated Merkel cells had a similar morphology when stained by either antiserum. Merkel-neurite complexes were clustered in relatively large numbers in the lingual gingiva, thus constituting structures closely similar to the 'touch domes' in the skin. Clusters of non-innervated cells showing the same immunohistochemical features as Merkel cells were also demonstrated. In other areas of the oral mucosa, the innervated and non-innervated elements were only occasionally seen but there were many encapsulated Meissner-like receptors. When comparing the two different antisera, anti-PGP 9.5 appeared to provide a more consistent labelling of small fibres inside the epithelium and of bulb-like terminals on Merkel cells.
Adolescent↗
Combined effect of aloe-emodin and chemotherapeutic agents on the proliferation of an adherent variant cell line of Merkel cell carcinoma.
Merkel cell carcinoma (MCC) has only limited sensitivity to chemotherapeutic agents. The aim of the study was to determine if members of the anthraquinone family could be used as adjuncts to increase the growth inhibiting effect of anticancer agents in MCC. An adherent variant of MCC was derived from a previously established MCC cell line suspension. Cells were characterized by immunocytochemical methods using specific antibodies against epithelial (low molecular weight cytokeratins and cytokeratin 20) and neuroendocrine (neuron-specific enolase, neurofilament protein, chromogranin A and synaptophysin) antigens. Emodin and aloe-emodin, members of the anthraquinone family, inhibited proliferation of the adherent MCC cells, with a slight advantage of aloe-emodin over emodin. Aloin had no effect on cell proliferation. The chemotherapeutic agents, cis-platinol (abiplastin), doxorubicin (adriablastin), and 5-fluorouracil, and the tyrosine kinase inhibitor STI 571, all independently inhibited the proliferation of adherent MCC cells. The addition of aloe-emodin potentiated their inhibitory effect, especially when low concentrations of the anticancer compounds were used. The antiproliferative action of STI 571 may be associated with the presence of anti-c-kit antibodies. The combined use of anticancer agents, especially at low concentrations, and aloe-emodin may be considered a preferable means for treating MCC.
Antineoplastic Agents↗
Recent progress in studies on Merkel cell biology.
Merkel cells ubiquitously distribute in the skin of vertebrates, from cyclostomes to mammals. It is well known that mammalian Merkel cells coupled with axon terminals of type I sensory nerve fibers form slowly adapting mechanoreceptors, Merkel endings, within the epidermis. However, there are still many unresolved problems in the biology of Merkel cells. We reviewed recently acquired knowledge about the histochemical nature of Merkel cell granules, the morphological heterogeneity of Merkel cells and the roles of neurotrophins and their receptors for the development and survival of the cells. We discuss the functional significance of Merkel cell granules and the heterogeneity of Merkel cell populations.
Adenosine Triphosphate↗
The Merkel cell--a member of the APUD cell system. Fluorescence and electron microscopic contribution to the neurotransmitter function of the Merkel cell granules.
Merkel cells of sinus hair follicles of nude mice were investigated by fluorescence and electron microscopy following pretreatment with amine precursors (L-Dopa, L-5-Hydroxytryptophan) and monoaminoxidase-inhibitors (Marsilid, Harmaline). Neither in control animals nor in pretreated animals any evidence for an involvement of Merkel cells in monoamine metabolism could be found. Therefore, the hypothesis that Merkel cells might share the most constant cytochemical characteristics of the cells of the APUD series, i.e., to take up amine precursors, should definitely be left. Following Harmaline treatment, however, Merkel cells were found fluorescent; cytophotometric analysis of the fluorescence emission spectra of formaldehyde-treated tissue ascertained that this fluorescence was due merely to a specific Harmaline fluorescence. The significance of Harmaline uptake in Merkel cells, most probably in the Merkel cell granules, is discussed.
5-Hydroxytryptophan↗
Cellular and subcellular distribution of 7B2 in porcine Merkel cells.
BACKGROUND: Merkel cells are neuroendocrine cells located in the skin and oral mucosa of various mammalian species. These cells express multiple peptides as well as serotonin. Although the precise function of Merkel cells is still unknown, different studies support its role as mechano-electric transducer. 7B2 granin (secretogranin V) is a polypeptide isolated from the pituitary gland and present in the dense-cored granules of neuronal and paraneuronal cells. METHODS: The expression of the 7B2 in Merkel cells of pig snout skin was analysed by immunohistochemical techniques. The streptavidin-biotin peroxidase complex procedure was employed for light microscopy. A postembedding method using immunoglobulin-colloidal gold complexes was employed for the ultrastructural studies. RESULTS: Immunoreactivity for 7B2 was observed in virtually all Merkel cells, both in epidermis and vibrissae. The immunostaining was shown in the basal side of cytoplasms where neuroendocrine granules were accumulated. Immunoelectron microscopy allowed us to demonstrate that 7B2 labelling was located on the electrondense granules. Nuclei and epidermal nerve terminals associated with merkel cells did not show immunoreactivity. CONCLUSIONS: The polypeptide 7B2 is present in the dense-cored granules of Merkel cells. This result is consistent with the possible role for 7B2 in secretory granules' processing. To our knowledge this is the first evidence of 7B2 protein in Merkel cells.
Animals↗
The role of NT-3 signaling in Merkel cell development.
Merkel cells originate from the neural crest. They are located in hairy and glabrous skin and have neuroendocrine characteristics. Together with A beta afferents, Merkel cells form a slowly adapting mechanoreceptor, the Merkel nerve ending, which transduces steady skin indentation. Neurotphin-3 (NT-3) plays important roles in neural crest cell development. We thus sought to determine whether neurotrophin signaling is essential for Merkel cell development in the whisker pad of the mouse. Our data indicate that at embryonic day 16.5 (E 16.5), NT-3 and its receptors, p75 neurotrophin receptor (p75NTR) and tyrosine kinase receptor, TrkC are not expressed at detectable levels in Merkel cells. After a perinatal switch, however, Merkel cells in whiskers of newborn mice are immunoreactive for p75NTR, TrkC and NT-3. Immunoreactivity of all three markers persists into adulthood. By contrast, innervating fibers are intensely p75NTR-immunoreactive in E16.5 whiskers, but no TrkC immunoreactivity is detected. At birth, and at 6 weeks of age, afferent fibers are intensely immunoreactive for both p75NTR and TrkC. In TrkC null whiskers, numerous Merkel cells are present at E16.5, and they are innervated. We draw three major conclusions from these observations: (i) NT-3 signaling through p75NTR or TrkC is not required for the development and prenatal survival of either a major subset or of all Merkel cells, (ii) the postnatal survival of Merkel cells is supported by autocrine or paracrine NT-3, rather than by neuron-derived NT-3, and (iii) Merkel cell-derived NT-3 is not a chemoattractant for innervating A beta fibers, but is likely to be involved in maintaining Merkel cell innervation postnatally.
Animals↗
Cytokeratin 20: a marker for diagnosing Merkel cell carcinoma.
Merkel cell carcinoma is an aggressive cutaneous neoplasm that is often difficult to diagnose because of its histologic and immunohistochemical similarity to metastatic oat cell carcinomas and other cutaneous neoplasms. Our purpose was to determine the utility of immunoperoxidase staining of cytokeratin 20 (CK 20), a newly discovered intermediate filament protein, in Merkel cell carcinomas and other cutaneous tumors. Sixty-one tumors were sectioned and stained with antibodies directed at CK 20. The staining of Merkel cell carcinomas was compared with metastatic oat cell carcinomas, lymphomas, squamous cell carcinomas, basal cell carcinomas, melanomas, metastatic carcinoids, spiradenomas, eccrine carcinomas, adenoidcystic carcinoma, sebaceous carcinomas, hidradenomas, sebaceous epitheliomas, trichoblastomas, mixed tumors, and metastatic adenocarcinomas. Nine of 10 Merkel cell carcinomas stained with antibody to CK 20. Two metastatic carcinomas to the skin were also positive. One hidradenoma and one squamous carcinoma exhibited focal staining, but were otherwise negative. All other tumors were nonstaining. Cytokeratin 20 is a sensitive and specific marker for Merkel cell carcinoma and is helpful in distinguishing between Merkel cell carcinoma and other malignant and benign neoplasms.
Biomarkers, Tumor↗
[A case of Merkel cell carcinoma; observation of Merkel cell like cells in culture].
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Aged↗
Neurotrophin-3 signaling in mammalian Merkel cell development.
Merkel cells are sensory cells of neural crest origin. Because little is known about the mechanisms that direct their differentiation, we have investigated the potential role of a candidate regulatory factor, neurotrophin-3 (NT-3). At embryonic day 16.5 (E 16.5), neither NT-3 nor its primary receptors, TrkC and p75NTR are expressed by Merkel cells in the murine whisker. At the time of birth, however, Merkel cells are immunoreactive for NT-3, TrkC and p75NTR. In TrkC null and NT-3 null mice, Merkel cells differentiate initially, but undergo apoptosis perinatally. These results show that NT-3 signaling is not required for the differentiation of Merkel cells, but that it is essential for their postnatal survival.
Animals↗
Non random cytogenetic changes characterize Merkel cell carcinoma.
Merkel cell carcinoma is a rapidly proliferating neoplasm of neuroectodermal origin presenting in skin. Karyotypes obtained in direct preparations of three Merkel cell carcinomas were analyzed and compared with six other tumors which were reported in the literature. Of the nine tumors studied so far, eight (89 per cent) showed structural abnormalities of chromosome 1. These abnormalities were in the form of trisomy for chromosome 1q22----ter. Furthermore, it was also observed that the breaks of these rearrangements on chromosome 1 occurred at the bands to which c-oncogenes N-ras (p31), L-myc (p32), c-src (p36), c-ski (q22-22), and the beta-subunit of the nerve growth factor (NGF) (p22) were localized. In addition to structural changes, five out of the nine tumors (55.5 per cent) were trisomic for chromosome 1. Merkel cell tumors are often confused with small cell carcinoma of lung or peripheral neuroepithelioma. The cytogenetic abnormalities such as rearrangement of chromosome 3p and t(11;22)(q23;q12) which characterize lung carcinoma and peripheral neuroepithelioma, respectively, were not seen in any of the nine Merkel cell tumors studied. Thus it appears that rearrangement of chromosome 1 was non-randomly associated with Merkel cell carcinoma. It is of interest to note that genes involved in neuronal development and or differentiation have been mapped to the bands at which breaks occurred in these tumors. The significance of these changes is briefly discussed.
Aged↗
[Radiotherapy in the treatment of Merkel cell tumors].
Merkel cell carcinomas are very rare (80 cases up to 1986) and very malignant; they have been known for 20 years only as "trabecular carcinomas". They do not rise from neural crests, and therefore are not apudomas, but from a staminal cell of the skin with neuroendocrine evolution. Merkel cell carcinomas must be distinguished from undifferentiated carcinomas of the skin, lymphomas, and oat cell carcinomas. Eight patients (46 to 86 years old) are presented, 4 males and 4 females, with 1 gluteal (the younger female patient), 3 head and 4 limb localizations of Merkel cell carcinoma. Radiotherapy was carried out after surgery in 7 patients and after biopsy in 1; local recurrences were already present in 3 cases, and lymph node metastases in 5; tumor doses were 36-65 Gy, administered with different techniques, i.e. roentgen therapy, telecobalt therapy, 192Ir curietherapy. Chemotherapy was used in 2 metastatic patients only. Four patients are alive and free of disease and 4 are dead; 3 of the living patients have been followed 3-26 months. The high risk of radiation damage (1 necrosis, 2 giant edemas, 1 severe fibrosis) recommends that large fields and high single and/or total radiation doses be avoided. In conclusion, surgery is diagnostic but not curative on account of the high risk of recurrence; radiotherapy is important because Merkel cell carcinomas are very radiosensitive. Due to easy lymphatic spread of this type of cancer, radiotherapy must include the regional lymph nodes (dose: 40-50 Gy). The role of chemotherapy is still to be assessed but many antiblastic drugs are effective.
Aged↗
Met enkephalin-like immunoreactivity in Merkel cells.
The Merkel cells from sinus hair follicles of rats were investigated by immunohistochemistry using different antisera against neuropeptides and gastroenteropancreatic (GEP)-hormones. For the first time it has been demonstrated that Merkel cells exhibit an immunoreactivity towards metenkephalin (methionine-enkephalin). The met-enkephalin immunoreactivity was restricted to Merkel cells and was not found in associated nerve axons or terminals. Denervation of Merkel cells did not affect the met-enkephalin immunoreactivity. Antisera leu-enkephalin (leucine-enkephalin) and other polypeptides did not produce an immunoreaction. The demonstration of met-enkephalin-like immunoreactivity supports the concept that the Merkel cell is a member of the paraneuronal system and a potential neuroreceptor cell.
Animals↗