Topoisomerase II-alpha expression in melanocytic nevi and malignant melanoma

Malignant melanoma (MM) is considered to be a chemotherapy-refractory tumor. New anti-cancer drugs (e.g. etoposide) that target DNA topoisomerases (e.g. topoisomerase II-alpha (topo II alpha)) show activity against a wide variety of solid tumors. In this study, we investigated the frequency and rate of labeling for topo II alpha in 163 MMs (primary and metastatic) and 67 melanocytic nevi to determine whether topo II alpha expression is elevated in MM. Primary MM exhibited significantly more frequent topo II alpha expression compared to benign nevi (86% vs. 56%, p=0.0001). The rate of topo II alpha labeling in dysplastic melanocytic nevi, radial growth phase MM, vertical growth phase MM and metastatic MM revealed significant differences amongst groups and a positive covariance with advancing stage (means: 0.3, 0.5, 5, and 8 '+' cells/hpf, respectively; r=0.3, all p less than or equal to 0.02). Topo II alpha labeling significantly correlated with increasing mitotic activity, depth of invasion and Clark's level, diminishing tumor infiltrating lymphocytes, and poor outcome (all p less than or equal to 0.01) in primary MM. For metastatic MM, a minority (30%) exhibited marked elevation of topo II alpha expression. These findings indicate topo II alpha as a potential therapeutic target and marker for MM. Immunohistochemical analysis of disseminated MM may allow for correlation with clinical response and enable selection of candidates sensitive for specific chemotherapy.