Loss of BMI-1 expression is associated with clinical progress of malignant melanoma

BMI-1 is a member of the Polycomb group of genes (PcGs) and is involved in embryonic gene regulation and maintenance of adult stem cells. It has been suggested that BMI-1 protein is important in cell cycle regulation, since both p16/INK4a and p14/ARF are downstream BMI-1 targets. BMI-1 has been implicated in the development and progression of several malignancies, but its role in melanocytic tumors of the skin is unknown. In the present study, using immunohistochemistry on 178 benign and malignant melanocytic lesions and two different antibodies, BMI-1 expression was reduced in melanomas compared with benign nevi. In established melanomas, loss of BMI-1 expression was associated with features of aggressive tumors, such as increased tumor cell proliferation, presence of necrosis and increased expression of both N-cadherin and beta(3)-integrin, indicating a more invasive and mesenchymal phenotype. Low BMI-1 expression was associated with low p14 and CDK4 but not with p16 expression. Low levels of BMI-1 expression were also significantly associated with decreased patient survival.