Skin layer-specific Melan-A expression during progression of human cutaneous melanoma: implications for diagnostic applications of the marker.

Melan-A is widely used in the diagnostics of human melanoma. The immunogenicity of this glycoprotein makes it a potential target in immunotherapy and several authors have suggested its potential as a prognostic factor. Up to now there has been no clear direct evidence of changes of Melan-A expression during the progression of melanoma. We have performed objective immunohistochemical assessment of the expression of Melan-A in benign naevi and melanomas at different stages of progression. Our results show a complex pattern of changes in the expression of Melan-A in melanomas depending on the location of melanoma cells within individual skin layers. The expression of the antigen during tumour progression significantly decreases for melanoma cells located in the granular/spinous layer (r=-0.94, P=0.02) and increases for the papillary layer (r=0.99, P=0.002) and reticular layer (r=0.89, P=0.04). It should also be emphasized that from the Clark II level of progression the melanomas can be detected with high sensitivity and specificity using a simple cut-off test based on the determination of Melan-A expression in tumour cells located within the papillary layer.