New Perspectives on Melanoma_ The Role of PAX3

Pax3 expression in melanocytes of normal adult skin a

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Unformatted text preview: (A). C) PAX3 (mouse monoclonal antibody, DSHB) and Ki67 co‐expressing melanocytes are also observed in the epidermis of the sun‐ exposed skin. Lines in (A), (B) and (C) demarcate epidermal‐dermal border (EDB) or epidermal surface (ES). D) Graph shows the distribution of differentiation marker expression in normal skin melanocytes with respect to melanocyte location (in epidermis, outer root sheath (ORS), or hair follicle bulb). 62 Chapter III – Medic and Ziman, 2010 This indicates that melanocytes, both follicular and epidermal, have a variable differentiation status: from less differentiated PAX3, MITF and HES1‐positive to more differentiated PAX3, MITF and MLANA‐positive. The observed PAX3‐ negative, MLANA‐positive epidermal melanocytes may represent mature terminally differentiated melanocytes. In addition, Yang and colleagues [20] have recently proposed that in UV‐treated skin TGF‐β signalling from keratinocytes is downregulated, which increases PAX3 expression in epidermal melanocytes and stimulates their proliferation. In order to check if PAX3‐positive melanocytes observed here are proliferating we co‐stained PAX3 with a marker of proliferation Ki67, and found 18.1% of epidermal melanocytes in samples of sun‐exposed skin (scalp) to be double‐labelled (Figure 3.3C). In contrast to this, in samples that had relatively little sun exposure (breast) one single double labelled cell was observed in the epidermis (accounting for 1.4% of PAX3‐positive cells). PAX3 in cell survival: Co­expression with BCL2L1 To further characterise the phenotype of PAX3‐positive melanocytes relative to melanoma cells, expression of an antiapoptotic factor BCL2L1 was assessed in PAX3‐positive cells (Figure 3.5A). We have observed that a similar proportion of PAX3‐positive cells were also BCL2L1‐positive in melanocytes of normal skin, in naevi and in melanoma cells in all of the samples analysed (Figure 3.5D). The exception is melanoma metastases, in which BCL2L1 was detected in only on...
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