Expression of DNA topoisomerase II alpha in melanocytic skin tumors

ABSTRACT

Topoisomerases are nuclear enzymes that modulate the topological structure of DNA in order to facilitate cellular events such as replication and transcripion. These enzymes are also the cellular targets of new classes of chemotherapy agents termed topoisomerase poisons. These drugs are showing activity against a wide variety of solid human neoplasms. However, malignant melanoma [MM] is considered to be a chemotherapy refractory tumor and the commonly used anticancer drugs do not seem to modify the prognosis of metastatic disease. Because of the challenges in treating MM, we performed an immunohistochemical study of this group of neoplasms to search for the presence of molecular marker that might indicate tumor response to topo II alpha active drugs. Forty- five patients with melanocytic skin tumors were the subjects of this study. They included 29 patients suffering from benign nevi, 4 dysplastic nevi and 12 MM. Topoisomerase II alpha expression showed significantly higher expression in MM cases than benign melanocytic nevi. Dysplastic nevi showed topo II alpha expression midway between the two extremities. The difference between the 3 groups was statistically highly significant p<0.0001. In MM cases, topo II alpha expression was significantly correlated with lymph node metastasis [p=0.001], tumor ulceration [p=0.001], tumor thickness [p=0.0001], Clark's level [p=0.008], and nodular type melanoma [p=0.003] In conclusion, expression of topo II alpha provides a useful marker for proliferation and can differentiate between benign and malignant melanocytic skin tumors. While in MM cases, it is considered as a poor prognostic marker. As the enzyme topo II alpha is the target of a group of cytotoxic drugs. its expression might serve to predict the success of adjuvant cytotoxic therapy especially in advanced MM cases