Expression of the endothelin-B receptor in pigment cell lesions of the skin - Evidence for its role as tumor progression marker in malignant melanoma

Endothelins (ETs) exert several functions in human melanocytes, including p roliferation, dendrite formation, and melanin synthesis. Among the ET recep tors, the non-selective endothelin-B (ETB) receptor is the major receptor i n melanocytes and malignant melanoma (MM) cells. In spite of the important role of ETs and their receptors in the growth and differentiation of melano cytes, the distribution and expression levels of ETB receptors in tissue se ctions of benign and malignant pigment cell lesions is still unknown. We co mbined immunohistochemistry and reverse transcriptase-polymerase chain reac tion (RT-PCR) to study ETB receptor expression in benign and malignant pigm ent cell lesions and in normal skin. Immunohistochemistry on paraffin-embed ded tissue sections of 159 cases revealed a significant increase in intensi ty of ETB receptor expression from common nevi over dysplastic nevi and pri mary MM to metastatic MM. Quantitative PCR using realtime detection on 75 s amples confirmed the immunohistochemical results. These data add the ETB re ceptor to the growing list of tumor progression markers in MM and suggest t hat ETs play a role in the progression of MM in the skin.