Expression of microtubule-associated protein 2 in benign and malignant melanocytes - Implications for differentiation and progression of cutaneous melanoma

Cutaneous melanocytic neoplasms are known to acquire variable characteristi cs of neural crest differentiation. Melanocytic nevus cells in the dermis a nd desmoplastic melanomas often display characteristics of nerve sheath dif ferentiation. The extent and nature of neuronal differentiation characteris tics displayed by primary and metastatic melanoma cells are not well unders tood, Here, we describe induction of a juvenile isoform of microtubule-asso ciated protein 2 (MAP-2c) in cultured metastatic melanoma cells by the diff erentiation inducer hexamethylene bisacetamide, Up-regulation of this MAP-2 isoform, a marker for immature neurons, is accompanied by extended dendrit ic morphology and down-regulation of tyrosinase-related protein 1 (TYRP1/gp 75), a melanocyte differentiation marker. In a panel of cell lines that rep resent melanoma tumor progression, MAP-2c mRNA and the corresponding simila r to 70-kd protein could be detected predominantly in primary melanomas. Im munohistochemical analysis of 61 benign and malignant melanocytit lesions s howed abundant expression of MAP-2 protein in melanocytic nevi and in the i n situ and invasive components of primary melanoma, but only focal heteroge neous expression in a few metastatic melanomas. In contrast, MAP-2-positive dermal nevus cells and the invasive cells of primary melanomas were TYRP1- negative, This reciprocal staining pattern in vivo is similar to the in vit ro observation that induction of the neuronal marker MAP-2 in metastatic me lanoma cells is accompanied by selective extinction of the melanocytic mark er TYRP1, Our data show that neoplastic melanocytes, particularly at early stages, retain the plasticity to express the neuron-specific marker MAP-2. These observations are consistent with the premise that both benign and mal ignant melanocytes in the dermis can express markers of neuronal differenti ation.