Immunohistochemical localization of muscarinic acetylcholine receptors in primary and metastatic malignant melanomas

In embryos morphogenetically active cells transiently express the cholinergic system comprising cholinesterase activity and muscarinic acetylcholine receptors. Malignant melanomas develop from melanocytes, which are derived from the neural crest. Neural crest cells express the embryonic muscarinic system during migration. Using the monoclonal antibody M35, we now show that normal melanocytes carry no muscarinic receptors, whereas malignant melanoma cells express them again. In primary melanomas and metastatic melanomas, we identified muscarinic receptors in solid strands or groups of atypical cells. In all primary malignant melanomas studied we found inhomogeneous distributions of M35-immunoreactivity subdividing the tumors into three different zones. In the tumor center, groups or single cells often showed only little or even no immunofluorescence. In contrast, pericentrally we detected strong immunostaining in the conglomerations of atypical melanocytes. In the peripheral infiltration zone, intensely fluorescent cells in clusters or single, were spreading into the normal tissue, leading to a more patchy staining pattern. Melanocytes of nevi also possess muscarinic receptors, showing similar distribution patterns as in the melanoma. We suggest that in malignant melanomas muscarinic receptors might play a regulative role in infiltrative growth and metastasis.