Nicotinic Acetylcholine Receptor Expression in Merkel Cell Carcinoma Is Associated With Clinical and Histopathologic Parameters.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy with neuroendocrine differentiation. Several molecular pathways have been implicated in MCC development and multiple cell-of-origin candidates have been proposed, including neural crest cells, which express acetylcholine receptors (AChRs). The role of nicotinic acetylcholine receptors (nAChRs) in MCC has not been explored. In this study, we investigated if MCC expresses nAChRs and if nAChR expression correlates with patient characteristics. METHODS: The study included 71 MCC cases diagnosed with sufficient tissue available to perform immunohistochemical analysis. The median follow-up was 29.8 months (range, 2.7-234.1). We performed immunohistochemistry using antibodies against the α3, α5, and α7nAChR subunits. RESULTS: Our results show that the majority of MCC cases expressed α3, α5, and α7-nAChR subunits. Of the 71 cases, 59 (83%) expressed α3-nAChR, 71 (100%) expressed α5-nAChR, and 63 (88%) expressed α7-nAChR. Location of immunoreactivity differed between cases and included cytoplasmic only and nuclear/peri-nuclear, with variation in the intensity of staining. There were significant correlations between the intensity or location of immunoreactivity and clinical and histopathologic parameters. CONCLUSIONS: These findings seem to support that MCC displays the features of neural crest cells, and suggest the potential for nAChR-targeted therapy.