MOLECULAR ANALYSIS OF MELANOMA PRECURSOR LESIONS

Atypical (dysplastic) nevi are melanocytic lesions, which are precurso rs of melanoma as well as markers of increased melanoma risk. Although these lesions exhibit distinct clinical and histological features, th eir molecular features are largely unknown. To determine whether atypi cal, compared to benign nevi, from patients with a clinical history of malignant melanoma reveal molecular changes, we analyzed these lesion s for the expression of two growth factors (basic fibroblast growth fa ctor and transforming growth factor alpha), their receptors (fibroblas t growth factor receptor-1 and epidermal growth factor receptor), and two cell adhesion molecules (MUC18 and alpha upsilon beta 3 integrin), all of which are expressed in primary and metastatic melanomas. The r esults demonstrated a statistically significant correlation (P = 0.02) between increasing degrees of histological atypia and expression of e pidermal growth factor receptor in the epidermal keratinocytes of atyp ical melanocytic lesions. Furthermore, both atypical and benign nevi r evealed considerably high levels of overall gene activity in their der mal melanocytic and epidermal keratinocytic compartments. In contrast, the epidermal-dermal junction wherein melanoma evolves showed little gene activity, suggesting that molecular events occurring adjacent to this junction may be important for melanocytic transformation.