IMMUNOHISTOCHEMICAL LOCALIZATION OF MUSCARINIC ACETYLCHOLINE-RECEPTORS IN PRIMARY AND METASTATIC MALIGNANT MELANOMAS

In embryos morphogenetically active cells transiently express the chol inergic system comprising cholinesterase activity and muscarinic acety lcholine receptors. Malignant melanomas develop from melanocytes, whic h are derived from the neural crest. Neural crest cells express the em bryonic muscarinic system during migration. Using the monoclonal antib ody M35, we now show that normal melanocytes carry no muscarinic recep tors, 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 malignan t melanomas studied we found inhomogeneous distributions of M35-immuno reactivity subdividing the tumors into three different zones. In the t umor center, groups or single cells often showed only little or even n o immunofluorescence. In contrast, pericentrally we detected strong im munostaining in the conglomerations of atypical melanocytes. In the pe ripheral infiltration zone, intensely fluorescent cells in clusters or single, were spreading into the normal tissue, leading to a more patc hy staining pattern. Melanocytes of nevi also possess muscarinic recep tors, showing similar distribution patterns as in the melanoma. We sug gest that in malignant melanomas muscarinic receptors might play a reg ulative role in infiltrative growth and metastasis.