P53 mutation in metastatic melanomas and primary melanomas from sun‐exposed and sun‐protected sites

Abstract

AbstractBackground p53 mutation has been observed in many human malignancies, including skin cancers. However, the data in melanoma has been conflicting.Material and methods We have examined, by immunohistochemistry, using the DO7 and CM1 antibodies, the frequency of p53 overexpression in 14 metastatic melanomas and 61 primary melanomas, of which 30 were from sun‐protected sites and 31 from sun‐exposed sites.Results Ten of 14 metastatic melanomas showed p53 overexpression compared to only eight of 61 primary melanomas (P < 0.004). No significant difference in p53 expression was found between primary melanomas from sun‐protected (2/30) and sun‐exposed sites (6/31). We have also examined p53 mutation by single‐strand conformation polymorphism (SSCP) analysis of four melanoma cell lines. One cell line established from a primary melanoma from a sun‐protected site showed evidence of an altered migration pattern in exon 7. Sequencing analysis of this region confirmed a point mutation in codon 244, showing a G to C transversion. This mutation is unlikely to be due to ultraviolet (UV) radiation since mutations caused by UV radiation are predominantly CC → TT or C → T transitions.Conclusions In summary, p53 mutation in primary melanoma is uncommon and does not appear to be related to UV radiation. p53 mutation is more common in metastatic melanomas suggesting that it may be involved as a late event in melanoma progression.