New Perspectives on Melanoma_ The Role of PAX3

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Unformatted text preview: onclusion Chapter VI – Conclusion Limitations of the study This study has conclusively shown continuous expression of the melanocytic developmental regulator, PAX3, in adult normal epidermal melanocytes [2], and this was also confirmed later by He and colleagues [18]. A study from the USA however, reports no PAX3 expression in normal skin and naevi, and expression is only observed in a small proportion of melanomas [24]. This discrepancy might be attributed to the methodology, but might also be a reflection of the geographic origin of the samples used for these studies. It has been shown that UV‐induced TGFβ reduction results in PAX3 upregulation and melanocyte proliferation, linking PAX3 expression to the extent of sun exposure [20]. There might therefore be a difference between melanoma and skin samples originating from the Northern vs the Southern hemisphere, related to the amount of sun exposure and UV radiation. The limitation of our study is that a relatively small number of normal skin samples were tested which originated from different anatomical locations. Additional normal skin samples, from both exposed and non sun‐exposed areas are required to address this anomaly. Another limitation of this study relates to the cell lines used for PAX3 target analysis. One metastatic melanoma cell line and one neonatal human epidermal melanocyte primary culture were used for the study. Neonatal melanocytes are known to exhibit different culturing capacity compared to adult epidermal melanocytes. On the other hand the A2058 melanoma cell line is a highly metastatic low pigmented cell line. Further experiments using additional cell lines, in particular adult epidermal melanocytes and a less aggressive melanoma cell line, might provide additional information. Results from this study provide, for the first time, several novel findings, such as a continuous expression of PAX3 across the whole range of melanocytic cells, from melanoblasts, throughout adult melanocytes, through to melanocyti...
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