Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.10.3.1 (tyrosinase)
 9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies of the human neuroblastoma cell line SK-N-SH had demonstrated the presence of and phenotypic interconversion (transdifferentiation) between two morphologically and biochemically distinct cell types: N (neuroblastic) cells with properties of noradrenergic neurons and S (substrate-adherent) cells with properties of melanocytes. Current studies have sought to test the generality of these findings among other cultured human neuroblastoma cell lines and to define further the S-cell phenotype and that of a newly identified, morphologically intermediate, I-type cell. Morphologically homogeneous populations (clonal sublines or subpopulations) of N, S, and I cells were isolated from five additional neuroblastoma cell lines and analyzed biochemically for neuronal, glial, and melanocytic marker enzyme activities and norepinephrine uptake. Immunoblot techniques were used to detect intermediate filament proteins (neurofilament protein, vimentin, glial fibrillary acidic protein) and fibronectin. All N-type cells exhibited neuronal marker enzyme activities, specific uptake of norepinephrine, and presence of one or more neurofilament proteins. S-type cells generally lacked neuronal characteristics but contained, instead, tyrosinase activity (a melanocytic marker enzyme), vimentin, and fibronectin. This combination of attributes is suggestive of a multipotent embryonal precursor cell of the neural crest. I-type cells differentially expressed both S- and N-cell properties and could represent either a stem cell or an intermediate in the transdifferentiation process. Studies of the biological significance of human neuroblastoma cell transdifferentiation and the molecular mechanisms underlying this process may be of relevance to the biological and clinical behavior of this tumor in the patient.
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PMID:Phenotypic diversification in human neuroblastoma cells: expression of distinct neural crest lineages. 253 91

A variety of cytomorphological features, architectural patterns and stromal changes may be observed in malignant melanomas. Hence, melanomas may mimic carcinomas, sarcomas, benign stromal tumours, lymphomas, plasmacytomas and germ cell tumours. Melanomas may be composed of large pleomorphic cells, small cells, spindle cells and may contain clear, signet-ring, pseudolipoblastic, rhabdoid, plasmacytoid or balloon cells. Various inclusions and phagocytosed material may be present in their cytoplasm. Nuclei may show bi- or multi-nucleation, lobation, inclusions, grooving and angulation. Architectural variations include fasciculation, whorling, nesting, trabeculation, pseudoglandular/pseudopapillary/pseudofollicular, pseudorosetting and angiocentric patterns. Myxoid or desmoplastic changes and very rarely pseudoangiosarcomatous change, granulomatous inflammation or osteoclastic giant cell response may be seen in the stroma. The stromal blood vessels may exhibit a haemangiopericytomatous pattern, proliferation of glomeruloid blood vessels and perivascular hyalinization. Occasionally, differentiation to nonmelanocytic structures (Schwannian, fibro-/myofibroblastic, osteocartilaginous, smooth muscle, rhabdomyoblastic, ganglionic and ganglioneuroblastic) may be observed. Typically melanomas are S100 protein, NKIC3, HMB-45, Melan-A and tyrosinase positive but some melanomas may exhibit an aberrant immunophenotype and may express cytokeratins, desmin, smooth muscle actin, KP1 (CD68), CEA, EMA and VS38. Very rarely, neurofilament protein and GFAP positivity may be seen.
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PMID:Morphological and immunophenotypic variations in malignant melanoma. 1079 80

Rosette formation is a feature that has not been described as occurring in melanocytic neoplasms. We present such a unique case. A 59-year-old man presented with an asymptomatic, soft, hairy 3.0 x 2.0-cm pigmented lesion that had been present for many years in the right external ear, extending from the conchal bowl onto the antitragus area. Examination of histologic sections showed a proliferation of nonatypical and heavily pigmented melanocytes in the superficial dermis and around deep adnexal structures, characteristic of a congenital nevus. In other areas, pigmented spindled and dendritic cells infiltrated thickened collagen bundles in a pattern of a blue nevus. A nodular proliferation of epithelioid melanocytes was seen within the deep dermis and subcutaneous tissue. The periphery of the nodule merged with the surrounding nevus cells. Neoplastic cells with nuclear atypia, melanin pigment, pseudonuclear inclusions, and balloon cell change were present. In addition, there was rosette formation by the tumor cells, with a central aggregate of coarse cell processes. Neuroid cords were also noted. No prominent mitotic figures, necrosis, or significant inflammatory infiltrate were noted. The neoplastic cells were positive for S-100 protein, Mart-1, tyrosinase, neuron-specific enolase, and vimentin. HMB-45 and Ki-67 (MIB-1) labeled only rare neoplastic cells within the proliferative nodule. The tumor cells were negative for synaptophysin, protein gene product 9.5, CD57, epithelial membrane antigen, CD31, and CD34. The central cell processes of the rosettes were negative for trichome, type IV collagen, neurofilament protein, glial fibrillary acidic protein, and tyrosine hydroxylase. We also retrospectively examined 78 congenital nevi of 65 pediatric patients at our institution. Rosette formation was not seen in any of these cases.
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PMID:Rosette formation within a proliferative nodule of an atypical combined melanocytic nevus in an adult. 1287 2

The authors describe 2 tumors that, to the best of their knowledge, are hitherto undescribed. The predominant cell type was small round to fusiform dark blue cells. The dark blue cells formed distinct epithelial cords with gland-like formations with mucicarmine-positive mucus. Another distinctive component of the tumors was a mesenchymal one. The mesenchymal areas appeared benign and could be likened to a fibroma having a densely collagenous stroma, or they had spindle cells set in the myxoid background, rendering a myxoma-like appearance. Another distinctive feature was ganglion cell differentiation. Mitotic figures, including atypical forms, were found only in the small cell component. All cells were immunohistochemically negative for actin, calponin, desmin, HMB45, neurofilament protein, CD99/MIC2, Melan A, tyrosinase, serotonin, CD56, Melan A, GFAP, and S-100 protein. Cytokeratin, synaptophysin, FLI1 protein, and chromogranin antibodies reacted only in the primitive small round cells, while all the other components were cytokeratin negative. Fluorescence in situ hybridization showed that the tumors are without the EWSR1 gene translocation and gain 12p. Ultrastructurally, the cells were endowed with well-formed intercellular desmosomes membrane-bound secretory in the cytoplasm. Granules were found in the cytoplasm. We suggest the name "primitive small cell tumor with epithelial, gangliocytic, neuroendocrine, and mesenchymal differentiation" for this neoplasm.
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PMID:Primitive small cell tumor with epithelial, gangliocytic, neuroendocrine, and mesenchymal differentiation: report of 2 cases. 1791 55

Malignant melanomas are known to express vimentin, among other intermediate filaments. Though anomalous keratin expression by malignant melanoma has been reported, its frequency is not well-established and this phenomenon is not well-known. We have seen in consultation a number of malignant melanomas with anomalous expression of keratin, other intermediate filaments, or synaptophysin, and therefore studied a large group of primary and metastatic melanomas to determine the frequency of these events. About 73 cases of malignant melanoma (22 primaries and 51 metastases) from 71 patients (51 male, 20 female; mean 59 years, range 17-87 years) were retrieved from our archives. Prior diagnoses were confirmed by re-review of hematoxylin and eosin sections and relevant (e.g., S100 protein, HMB45, Melan-A, and tyrosinase) immunohistochemical studies. Available sections were immunostained for keratin (OSCAR and AE1/AE3 antibodies), desmin, neurofilament protein, glial fibrillary acidic protein, synaptophysin, and chromogranin A. Not all cases could be tested for all markers. Cases were predominantly epithelioid (48/73, 66%) or spindle cell/desmoplastic (25/73, 34%). S100 protein, Melan-A, HMB45, and tyrosinase were positive in 60/65 (92%), 34/64 (53%), 30/60 (50%), 25/48 (52%) of cases, respectively. All five S100-protein-negative cases expressed at least one of the other melanocytic markers: Melan-A (two of four, 50%), HMB45 (two of three, 67%), and tyrosinase (one of two, 50%). All cases expressed at least one melanocytic marker. Cases were positive for keratin (OSCAR, 17/61, 28%; AE1/AE3, 16/40, 40%), desmin (11/47, 24%), neurofilament protein (5/31, 16%), glial fibrillary acidic protein (3/32, 9%), and synaptophysin (10/34, 29%), typically only in a minority of cells. Chromogranin was negative (0/32, 0%). Altogether 9/73 cases (12%) showed expression of >1 intermediate filament. All S100-protein-negative melanomas showed anomalous intermediate filament expression (keratin--one case, desmin--three cases, neurofilament protein--one case). Anomalous intermediate filament or synaptophysin expression was more common in epithelioid (intermediate filament, 27/48, 56%; synaptophysin, 7/22, 32%) as compared with spindle cell/desmoplastic (intermediate filament, 8/25, 32%; synaptophysin, 3/12, 25%) melanomas. Overall, 48% (35/73) of cases showed anomalous expression of at least one intermediate filament. Anomalous expression of all intermediate filaments and synaptophysin was found in significant subsets of malignant melanoma, representing potentially serious diagnostic pitfalls. While the inclusion of consultation cases may inflate the frequency of these findings in this series, similar findings were also seen in institutional cases. Malignant melanoma showing anomalous intermediate filament and synaptophysin expression may easily be mistaken for carcinomas, rhabdomyosarcomas, and neuroendocrine tumors. Awareness of this phenomenon, careful histopathological evaluation, and an appropriate melanocytic immunohistochemical panel should facilitate the diagnosis of malignant melanoma with unusual immunophenotypes.
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PMID:Aberrant intermediate filament and synaptophysin expression is a frequent event in malignant melanoma: an immunohistochemical study of 73 cases. 2602 51