Prognostic significance of LKB1 promoter methylation in cutaneous malignant melanoma.

Liver kinase B1 (LKB1) loss is a common occurrence in various types of human cancer, and promoter methylation has been hypothesized to be a major mechanism of LKB1 inactivation. The association between LKB1 gene promoter methylation status and tumor progression in cutaneous malignant melanoma (CMM) remains unknown. In the present study, the methylation status of the LKB1 promoter region was examined in 57 human cutaneous malignant melanomas and 50 benign skin lesion controls by methylation-specific polymerase chain reaction. Consequently, 12 (12/57) melanoma tissues exhibited LKB1 promoter methylation, while only 2 (2/50) benign lesions presented with LKB1 hypermethylation. The frequency of LKB1 promoter methylation in melanoma was significantly increased compared with the benign controls (P<0.05). Additional statistical analysis demonstrated that hypermethylation of the LKB1 gene was correlated with Breslow's thickness, presence of ulceration and American Joint Committee on Cancer stage (P<0.05). Additionally, Kaplan-Meier analysis revealed that LKB1 hypermethylation was significantly associated with poorer survival (P<0.01). Multivariate COX regression analysis indicated that LKB1 promoter methylation was an independent prognostic factor for overall survival in patients with melanoma.