Evidence that the p75 neurotrophin receptor mediates perineural spread of desmoplastic melanoma

Background: The desmoplastic variant of melanoma has a striking propensity for neurotropism. This neurotropism may reflect Schwannian differentiation. The migration of Schwann cells along embryonic nerves is reportedly regulated by the 75 kd neurotrophin receptor (p75(NTR)) and one of its cognate Ligands, nerve growth factor (NGF). Objective: The purpose of this study was to test the hypothesis that the mechanism of perineural spread in desmoplastic melanomas is analogous to that of neurotropism in Schwann cells, which apparently depends on expression of p75 neurotrophin receptor and its ligands. Methods: Immunolabeling of p75(NTR) in histologic sections of spindle cell and desmoplastic melanomas was compared and contrasted with that of epithelioid melanomas. Results: The histologic material consisted of spindle cell melanoma specimens from 11 patients, of which seven exhibited features of desmoplastic melanoma. All spindle cell melanoma specimens expressed the p75(NTR) in at least 10% of the cells, and most expressed p75(NTR) in more than 50% of cells. in contrast, 10 of 11 control melanomas of conventional epithelioid phenotype expressed lower levels of p75(NTR) (0% to 10% of cells). Conclusion: There is a strong correlation between expression of p75(NTR) and the desmoplastic phenotype, supporting the hypothesis that the propensity of these melanomas for neurotropism involves p75(NTR) and its ligands. Immunolabeling for p75(NTR) may be a useful marker for the neurotropic phenotype, as well as for detecting perineural spread in histologic sections of melanomas.