Abstract:

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous malignancy, with 5-year survival rates as low as 14% in patients with metastases. Mechanisms driving MCC include integrated Merkel cell polyoma virus (MCPyV) and high ultraviolet light-induced somatic mutational burden (specific to MCPyV-negative MCCs). Possible cells of origin of MCC include dermal pluripotent stem cells and neural crest cells which express acetylcholine receptors (AChRs), critical for their migration during development. Reports demonstrate neural crest derived melanoma and numerous non-Merkel cell neuroendocrine tumors express AChRs. Nicotinic AChR (nAChRs) ? -9 and -5 have been proposed to play a role in melanoma. However, the role of nAChRs in MCC has not been explored. We hypothesized that MCC cases would express nAChRs, and that expression patterns would correlate with patient clinical outcomes and histopathologic parameters. We reviewed 45 cases of MCC with available tissue blocks diagnosed at our institution between 2000 and 2019 and collated the clinical and histomorphologic data. After appropriate validation, immunohistochemical (IHC) studies were performed using anti-nAChR ?-5 antibody (D-11) [Santa Cruz Biotechnologies]. We assessed the pattern, proportion, and intensity of IHC expression and found that all the cases of MCC were immunoreactive for the ?-5 antibody with varying intensity. There was variation in the pattern of staining; cytoplasmic (n=13), nuclear (n=7), and mixed nuclear and cytoplasmic (n=25). Our preliminary findings show that the correlation between the pattern of immunoreactivity and MCPyV status trended towards statistical significance (p=0.08), with none of the MCPyV-negative cases showing nuclear-only positivity. We concluded that nAChRs are expressed in MCC and hypothesize there may be a correlation between MCPyV status and the pattern of expression of nAChR. Studies using a larger sample size and additional antibodies (nAChR ?-3, 7 and 9) are ongoing.

Financial Disclosure:
No current or relevant financial relationships exist.

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Christopher Cunningham, MD