New Perspectives on Melanoma_ The Role of PAX3

Mcamcanmediatebothhomotypic adhesion between melanoma

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Unformatted text preview: wing overall number of PAX3, MCAM double‐ labelled cells in normal skins, naevi, primary melanomas and melanoma metastases. Each column represents a percentage of PAX3‐positive cells that are also MCAM‐positive, averaged across all samples. 66 Chapter III – Medic and Ziman, 2010 Discussion PAX3 expression in normal skin, naevi and melanoma In agreement with previous reports, we confirm here that PAX3 is expressed inall melanoma and naevi samples analysed. There is however a paucity of studies analysing PAX3 expression in differentiated melanocytes in human skin. Traditionally considered a critical embryonic regulator, PAX3 has been suggested to maintain melanocyte stem cells in the bulge area of the hair follicles in mice [19], but was thought to be downregulated upon terminal differentiation of melanocytes. This belief has been supported by reports detailing absence of PAX3 expression in melanocytes of normal human skin in contrast to naevi and melanomas [24,25]. Our results show conclusively that PAX3 is expressed in both epidermal and follicular melanocytes of human skin. Furthermore, co‐expression with MITF confirms the melanocytic origin of these PAX3‐positive cells. We also show here, for the first time, the variable phenotype of epidermal melanocytes of normal skin. The observed frequency of PAX3 expression in naevi, melanomas and specifically in melanocytes in normal skin is much higher that reported elsewhere [24,25]. One possible explanation could be the methodology we used, mainly EDTA/Tris antigen retrieval buffer, rather than the citrate buffer commonly used by other researchers, which was, in our experience, less efficient. It might also reflect the influence of environmental factors, namely sun exposure and solar radiation. It has recently been suggested that in UV‐treated skin TGF‐β signalling from keratinocytes is downregulated, increasing PAX3 expression in epidermal melanocytes thus stimulating their proliferation [20]. All the samples used in this study are collected from people living in Australia, where the solar radiation levels are in the high to...
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