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)

PEComas are mesenchymal neoplasms composed of perivascular epithelioid cells (PEC) and include a spectrum of tumors. PEComas and malignant melanoma share common morphological, immunohistochemical, and ultrastructural features, such as epithelioid cell morphology and melanocytic immunophenotype. Melanocytic markers commonly expressed in PEC tumors include HMB-45, Melan-A/MART-1, tyrosinase, microphthalmia transcription factor (MITF), and occasionally, S100. Given this morphological and immunophenotypical overlap, the differential diagnosis between a PEComa and malignant melanoma can represent a challenge. Additional diagnostic difficulty is the differentiation of melanoma and PEComa from clear cell sarcoma that is indistinguishable from melanoma based on the immunohistochemical profile. Recent studies have shown that MUM-1, a known lymphocyte marker shows positive immunostaining in nevi and melanomas, its expression in PEComas and clear cell sarcoma, however, has not been previously addressed. In this study, the authors analyzed MUM-1 expression using immunohistochemistry in PEComas (n = 8), the PEComa family members, angiomyolipomas (n = 13), and clear cell sarcomas (n = 11) and compared the staining pattern with malignant melanomas (n = 25), both primary (n = 14) and metastatic (n = 11). It was found that 92.3% of primary melanomas and 81.3% of metastatic melanomas were MUM-1 positive. In contrast, MUM-1 was only weakly positive in only 25% of PEComas and negative in all angiomyolipomas. MUM-1 expression was noted in 72.7% of clear cell sarcomas. The study demonstrated differential MUM-1 expression between PEComas and other true melanocytic tumors and suggested that the addition of MUM-1 to the usual panel of melanocyte markers could be a helpful adjunctive study to aid in the differential diagnosis between these entities.
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PMID:MUM-1 expression differentiates tumors in the PEComa family from clear cell sarcoma and melanoma. 2190 80

Recently, a small subgroup of PEComas has been recognized to harbor rearrangements involving TFE3, a gene also involved in rearrangements in translocation-associated renal cell carcinomas and alveolar soft part sarcomas. The few TFE3 rearrangement-associated PEComas reported have exhibited distinctive pathologic characteristics contrasting to PEComas in general, including predominantly epithelioid nested or alveolar morphology and underexpression of muscle markers by immunohistochemistry. In this study, we report the clinicopathologic, immunohistochemical, and molecular features of a primary urinary bladder PEComa diagnosed by transurethral resection in a 55-year-old woman that clinically mimicked urothelial carcinoma. Light microscopy demonstrated mixed spindle cell and epithelioid morphology with the epithelioid component preferentially associated with blood vessels. Immunohistochemistry revealed positive staining for HMB45, tyrosinase, MiTF, cathepsin K, smooth muscle actin, and TFE3 protein. Fluorescence in situ hybridization for the TFE3 gene revealed a split signal pattern, indicating TFE3 rearrangement. X chromosome inactivation analysis demonstrated a clonal pattern despite the heterogenous appearance of the tumor. Unfortunately, despite surgical resection and sarcoma-directed therapy, the patient died of metastatic disease 12 months after diagnosis. This report adds to the known data regarding urinary bladder PEComas and PEComas with TFE3 rearrangement, indicating that both can pursue an aggressive course. Although the few reported TFE3-rearranged PEComas have predominantly lacked a spindle cell component and expression of smooth muscle actin and MiTF by immunohistochemistry, the findings in this study indicate that these features are sometimes present in TFE3-rearranged PEComas.
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PMID:Malignant perivascular epithelioid cell neoplasm (PEComa) of the urinary bladder with TFE3 gene rearrangement: clinicopathologic, immunohistochemical, and molecular features. 2379 24

Mammalian pigmentation requires the production of melanin by melanocytes and its transfer to neighboring keratinocytes. These complex processes are regulated by several molecular pathways. Melanophilin ( MLPH) and WNT family member 1 ( WNT1), known to be involved in melanin transfer and melanin production, respectively, were predicted to be targets of microRNA-5110 using bioinformatics. In the current study, we investigated the effects of microRNA-5110 on pigmentation in alpaca ( Vicugna pacos) melanocytes. In situ hybridization identified high levels of microRNA-5110 in the cytoplasm of alpaca melanocytes. Luciferase activity assays confirmed that MLPH and WNT1 were targeted by microRNA-5110 in these cells. Overexpression and knockdown of microRNA-5110 in alpaca melanocytes downregulated and upregulated MLPH and WNT1 expression at the mRNA and protein levels, respectively. In addition, overexpression and knockdown of microRNA-5110 in alpaca melanocytes decreased and increased, respectively, the mRNA levels of the melanin transfer-related genes, rat sarcoma (RAS)-associated binding ( RAB27a) and myosin 5a ( MYO5a); the mRNA levels of microphthalmia-associated transcription factor ( MITF), tyrosinase ( TYR), and tyrosinase-related protein ( TYRP) 1; and the production of total alkali melanin and pheomelanin. In contrast, overexpression and knockdown of microRNA-5110 increased and decreased the mRNA levels of TYRP2, respectively. Overexpression of microRNA-5110 also increased eumelanin. These results indicate that microRNA-5110 regulates pigmentation in alpaca melanocytes by directly targeting MLPH and WNT1 to affect eumelanin production and transfer.-Yang, S., Liu, B., Ji, K., Fan, R., Dong, C. MicroRNA-5110 regulates pigmentation by cotargeting melanophilin and WNT family member 1.
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PMID:MicroRNA-5110 regulates pigmentation by cotargeting melanophilin and WNT family member 1. 2973 92

Melanoma is one of the great mimickers in pathology because it has diverse morphologies and can be mistaken for carcinoma or sarcoma. In most cases, immunochemistry is helpful in supporting the diagnosis and excluding other differentials. However, metastatic melanoma may lose immunohistochemical melanocytic markers and express nonmelanocytic lineage markers, which often poses a diagnostic dilemma and may be misdiagnosed as a poorly differentiated carcinoma or sarcoma. We report the case of a 52-year-old woman who had a history of recurrent melanoma on her right shoulder with axillary lymph node metastasis (BRAF V600K-mutated melanoma) and right-side breast-invasive ductal carcinoma (stage pT1b N0sn). One year later, she presented with a left-sided chest wall mass and enlarging left axillary lymph nodes. Needle core biopsies were obtained from both lesions, and histologic examination showed a poorly differentiated tumor with pleomorphic/anaplastic morphology and necrosis. The tumor cells were strongly immunoreactive for GATA-3 without expression of melanocytic markers (S100, Melan A, HMB45, SOX10, MITF, and tyrosinase). The history of melanoma prompted molecular analysis, and the lesion was found to harbor the BRAF V600K mutation, consistent with metastatic dedifferentiated melanoma. Recognition of metastatic dedifferentiated melanoma is important to avoid misdiagnosis of carcinoma, especially in patients with a previous history of carcinoma.
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PMID:Dedifferentiated Melanoma With Expression of Cytokeratin and GATA3 in a Patient With History of Breast Carcinoma. 3056 18


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