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New Perspectives on Melanoma_ The Role of PAX3

For immunofluorescent staining the following

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Unformatted text preview: tive epidermal melanocytes are also HES1‐positive, indicating they are not terminally differentiated. In summary, it seems that epidermal melanocytes are not all terminally differentiated and similar to those in the hair follicle they exhibit variable differentiation status, with a persistent PAX3 expression. Melanocytes in the ORS of the hair follicle are mostly PAX3 and MITF‐positive and not all are fully differentiated (23.7% HES1‐positive, 61.5% MLANA‐positive). In the matrix of the hair bulb the number of PAX3‐positive melanocytes is lower (around 65%), with only a small proportion still showing a less differentiated phenotype (10.5% HES1‐ positive and 36% MLANA‐positive). Epidermal PAX3‐positive melanocytes show a 69 Chapter III – Medic and Ziman, 2010 similar profile to those in the ORS (27.9% HES1‐positive, 62% MLANA‐positive). Interestingly, there are a similar number of MLANA‐positive (but PAX3‐negative) melanocytes in the epidermis (30.5%) and the hair matrix (40%), in contrast to the ORS where such cells are rare (3.9%). PAX3 expression seems to correlate with undifferentiated (co‐expressing HES1 and MITF) and differentiating (co‐ expressing MLANA and MITF) cells, whereas it might be diminished in terminally differentiated cells (PAX3‐negative but MLANA or MITF‐positive) that are further along the continuum of differentiation. It is possible that PAX3 is involved in maintenance of melanocyte “stemness”, at least while they are migrating towards their destination, either in the hair follicle or the epidermis. PAX3 in apoptosis It is also very likely that PAX3 is involved in keeping melanocytes alive, since three quarters of epidermal and more than half ORS and matrix PAX3‐positive melanocytes show expression of the PAX3 target, antiapoptotic BCL2L1. PAX3 is previously reported as an antiapoptotic regulator in tumours, including melanoma [28,155,156,160‐162]. Several known antiapoptotic factors, such as tumour suppressors p53, PTEN and BCL2L1, are invol...
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