Abstract

Alterations in cell cycle proteins involved in G1/S transition are implicated in melanocytic tumor progression and can have a potential role in target-based therapy and prognostication of melanoma. Cyclin D1 and Cyclin-Dependent Kinases (CDK) are critical for the proper function of the Retinoblastoma gene (Rb) and P53 gene which regulate the main checkpoints of G1/S transition in the cell cycle. Method: 38 cases of melanoma were evaluated to study correlation between Cyclin D1 expression by immunohistochemistry and depth of invasion if present as a primary outcome. Secondary outcomes include assessment of the relationship between immunohistochemical expression of Cyclin D1 and (status of surgical margins, histological type, lymphovascular invasion, perineural invasion, infiltrating lymphocytes, tumor regression, Clark level, lymph node metastasis, and number of mitotic figures per 1 mm²). Cyclin D1 is graded as follow: 0-negative, +1: <25%, +2: 25-50%, +3:50-75%, +4 >75%. Quantitative estimation of Cyclin D1 immunohistochemical expression is evaluated by two researchers independently to reach a consensus level of interpretations. Differences in Cyclin D1 expression were tested using chi-square tests for categorical variables and nonparametric Krukal-Wallis tests for continuous variables. Results: Depth of invasion of melanoma is significantly correlated with increasing Cyclin D1 immunohistochemical expression (p=.002). The number of Mitosis per mm² increases with increasing Cyclin D1 immunohistochemical expression (p=.011). Cyclin D1 was not significantly associated with other variables (p-value > .05). We conclude that these results support the rule of Cyclin D1 as driving mutation in melanoma.