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New Perspectives on Melanoma_ The Role of PAX3

Pax3 waspreviouslyreportedtorepress

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Unformatted text preview: hanges in PAX3 expression were associated with melanoma progression [2]. Our results showed persistent PAX3 expression across all melanocytic lesions. When assessed by RT‐qPCR, PAX3 expression was similar in naevi and primary melanoma samples, and significantly upregulated in melanoma metastases. However, these results reflect the overall increase in the number of PAX3‐expressing melanoma cells in samples of melanoma metastasis, rather than levels of expression per cell. Immunohistochemical analysis showed no significant correlation between level of PAX3 protein per cell and melanoma progression. Both intensity of PAX3 staining and frequency of PAX3‐expresing cells, relative to a known melanocytic marker MITF, showed similar results for primary melanomas as for naevi and melanocytes. By contrast, metastatic samples showed slightly lower PAX3 staining intensity per cell but the overall number of PAX3‐positive cells increased. 96 Chapter V – General Discussion Interestingly, we also observed consistent PAX3 expression in normal melanocytes, including epidermal melanocytes presumed to be terminally differentiated mature cells [2]. This was in contrast to the widely accepted belief that this developmental regulator is ‘switched off’ in differentiated adult melanocytes, and re‐expressed or aberrantly expressed in melanoma [19,20,24,25]. Several conflicting reports created uncertainty as to whether PAX3 expression is retained in adult melanocytes, with only a handful of reports detailing PAX3 expression in human primary melanocytes [16,17]. By contrast, murine primary melanocytes were shown to lack endogenous Pax3 [163]. A detailed study done by He and colleagues [18] confirmed our findings that PAX3 expression is retained in human epidermal melanocytes. This essentially posed a new question‐ what is the role of PAX3 in differentiated adult melanocytes? Moreover, does PAX3 persistent expression in melanocytes contribute to melanoma‐genesis and progression? The likelihood exists that the same developmental roles for PAX...
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