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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent advances in mouse genetics have identified molecular changes that are critical for melanocyte maturation and differentiation. This review briefly summarizes the current knowledge of distinct steps in melanocyte development, and identifies for each step the most important molecules such as the growth factors stem cell factor and endothelin-3, with their respective receptors. Classical cadherins, i.e. E-cadherin, N-cadherin and P-cadherin, determine melanocyte positioning in the skin. During naevus and melanoma development, the two growth factor signalling pathways are downregulated, whereas cadherin expression shifts concomitantly with re-positioning of the naevus and melanoma cells in the skin. Loss of E-cadherin and gain of N-cadherin by melanoma cells has profound consequences for the regulatory cross-talk between various types of cells in the skin. Naevus and melanoma cells that do not express E-cadherin are resistant to control by keratinocytes and establish close communications with fibroblasts and endothelial cells. However, forced expression of E-cadherin in melanoma cells can reverse the malignant phenotype by re-establishing the control of keratinocytes over the melanoma cells. Even highly aggressive metastatic melanoma cells can be signalled to turn off the expression of genes associated with tumour invasion and metastasis, suggesting that this strategy could be utilized in the therapy of melanoma.
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PMID:Lessons from melanocyte development for understanding the biological events in naevus and melanoma formation. 1098 64

In the tissue integration of melanocytes and melanoma cells, an important role is attributed to cell adhesion molecules, notably the cadherins. In cultured melanoma cells, we have previously described a more heterogeneous repertoire of cadherins than normal, including some melanoma subtypes synthesizing the desmosomal cadherin, desmoglein 2, out of the desmosomal context. Using biochemical and immunological characterization of junctional molecules, confocal laser scanning, and electron and immunoelectron microscopy, we now demonstrate homo- and heterotypic cell-cell adhesions of normal epidermal melanocytes. In human epidermis, both in situ and in cell culture, melanocytes and keratinocytes are connected by closely aligned membranes that are interspersed by small puncta adhaerentia containing heterotypic complexes of E- and P-cadherin. Moreover, melanocytes growing in culture often begin to synthesize desmoglein 2, which is dispersed over extended areas of intimate adhesive cell-cell associations. As desmoglein 2 is not found in melanocytes in situ, we hypothesize that its synthesis is correlated with cell proliferation. Indeed, in tissue microarrays, desmoglein 2 has been demonstrated in a sizable subset of nevi and primary melanomas. The biological meanings of these cell-cell adhesion molecule arrangements, the possible diagnostic and prognostic significance of these findings, and the implications of the heterogeneity types of melanomas are discussed.
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PMID:Subtypes of melanocytes and melanoma cells distinguished by their intercellular contacts: heterotypic adherens junctions, adhesive associations, and dispersed desmoglein 2 glycoproteins. 1897 6

Thirteen melanocytic skin neoplasms with a consultation diagnosis by A. Bernard Ackerman were submitted to immunohistochemistry for HMB-45, Ki67, cyclin D1, e-cadherin, and p16; 9/13 cases underwent fluorescence in situ hybridization (FISH) test targeting 6p25 (RREB1), 6q23 (MYB), centromere 6 (Cep6), and 11q13 (CCND1), as well as the centromere 7 (Cep7). A "consensus diagnosis" among 3 experts was also advocated both before and after morphomolecular information. Three neoplasms with a consultation diagnosis of Spitz nevus showed at least 3 abnormal immunohistochemical patterns; 2 of these cases were also FISH-positive for CCND1 gain, but none of them had a final consensus diagnosis of melanoma. Two neoplasms with a consultation diagnosis of congenital nevus received a consensus diagnosis of melanoma. Molecular morphology techniques can highlight the atypical features of melanocytic neoplasms and support existence of a morphobiologic "spectrum": This should be mirrored in the final report by abandoning the dichotomic (benign vs malignant) diagnostic approach.
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PMID:The impact of molecular morphology techniques on the expert diagnosis in melanocytic skin neoplasms. 2377 23