Osteopontin in Melanocytic Lesions—A First Step Towards Invasion?

Abstract

Determination of the earliest molecular changes that occur during the process of cellular transformation is of intense interest to the field of tumor biology but represents a considerable technical challenge in that it is not normally amenable to pathological examination. As the transition from melanocyte hyperplasia to primary cutaneous melanoma often occurs within dysplastic nevi at the dermal–epidermal junction on sun exposed sites of the skin, it presents a unique opportunity to examine these initial stages of tumor progression. Aberrant changes associated with this transition can be identified via gene expression profiling using high-density DNA microarrays probed with samples prepared from melanocytic lesions or cell lines (Carr et al, 2003) or conversely using immunohistochemical staining to determine expression in tissue section microarrays from defined stages (Pacifico et al, 2004). Genes identified as being differentially expressed in this way provide prognostic markers as well as insight into the process of cellular transformation. The combination of both of these techniques were used in the report ofZhou et al (2005), in order to discover genes highly upregulated in melanocytic lesions. Comparison of metastatic tumor nodules with benign nevi has found over 190 genes potentially implicated in this process of early stage transformation, with the osteopontin gene already recognized for its involvement in transformation of a number of diverse tumor types (Wai and Kuo, 2004) showing the highest abundance of differential expression.