The effect of the sun on expression of ß-catenin, p16 and cyclin d1 proteins in melanocytic lesions

Abstract

Background. The tumour suppressor gene product, p16, is often inactivated during melanoma malignant progression. Although the importance of p16 in melanomas is well documented, its relationship with cyclin D1, ß-catenin and ultraviolet radiation (UVR) remains unclear. Aim. To determine the role of these cell cycle-related proteins and high-risk sun exposure in the biological behaviour of melanocytic lesions. Methods. We used immunohistochemistry to examine 28 melanocytic naevi (MN; 9 congenital and 19 acquired types) and 24 primary cutaneous malignant melanomas (CMM; 19 nodular melanomas, 3 lentigo maligna melanomas, 1 acral lentiginous melanoma and 1 superficial spreading melanoma) for the presence of p16, cyclin D1 and ß-catenin. The melanocytic lesions were classified into two groups to examine the effects of UVR on these three proteins: high risk of sun exposure (chronically sun damaged; CSD), or low risk of sun exposure (nonchronically sun damaged; non-CSD). We evaluated the relationship between the production of these proteins and the histopathological and clinical characteristics of the lesions. Results. Production of p16 was repressed in most CMM, but not in MN (P < 0.0001). Cyclin D1 was overproduced in CMM but not in MN, and ß-catenin was frequently overproduced both in MN and CMM. Overproduction of ß-catenin was not common in CSD melanocytic lesions, but was more frequent in non-CSD melanocytic lesions (P = 0.027). Conclusion. An immunohistochemical panel including melanocytic markers enriched by p16 and cyclin D1 could be used to differentiate some borderline melanocytic lesions. In addition, the Wnt/ß-catenin pathway was more frequently activated in non-CSD than in CSD melanocytic lesions. © 2007 The Author(s).