Increased CDK4 protein expression predicts a poor prognosis in mucosal melanoma associated with the p16INK4a-CDK4-pRb pathway.

: Mucosal melanoma (MM) occurs in non-cutaneous mucosal sites, e.g., the head and neck or the lower genital tract; it is a rare and aggressive neoplasm with a poor prognosis. To date, few prognostic markers of MM have been well-defined. The aim of this study is to clarify the prognostic value of the cell-cycle regulatory proteins (CDK4, pRb and CyclinD1, p16) which are associated with the p16INK4a-CDK4-pRb pathway in MM. A total of 54 MM samples were obtained from biopsy specimens, and the expressions of the cell-cycle regulatory proteins (CDK4, pRb and CyclinD1, p16) were assessed by immunohistochemistry. A Mantel-Cox regression analysis was performed to investigate the association of these proteins with the overall survival of MM patients. Increased CDK4 expression was significantly associated with reduced survival at three years (P = 0.022). Increased CDK4 protein expression may be a helpful prognostic indicator for the management of these patients who infiltrate into the p16INK4a-CDK4-pRb pathway. In addition, we found that those patients with low expression of CDK4 were significantly older (P < 0.05) compared to the patients with high expression of CDK4.