Expression of Mismatch Repair Proteins in Merkel Cell Carcinoma

Simple Summary Merkel cell carcinoma (MCC) is a rare and highly malignant skin cancer with neuroendocrine differentiation. About 80% are Merkel cell polyomavirus (MCPyV) positive. The aim of this work was to immunohistochemically investigate the expression of mismatch repair proteins (MSH2, MSH6, MLH1, and PMS2) in MCC (n = 56). In a second step, tumors with a low expression were tested for microsatellite instability. Microsatellite instability in MCC could have an impact on immune checkpoint inhibitor therapy (ICI) outcome. This study showed a significant association between low expression of mismatch repair proteins and a negative MCPyV status. Microsatellite instability was detected in only one case. Future studies will establish whether this subset of MCC patients respond better to ICI. We aimed to assess for the first time the mismatch repair (MMR) protein expression in Merkel cell carcinoma (MCC). Immunohistochemistry was performed for MLH1, MSH2, MSH6, and PMS2 on patients' tumor tissue (n = 56), including neighbored healthy control tissue. In cases with low-level MMR expression ( 0.05). MCC appears to be a malignancy characterized by low-level MMR rather than completely deficient MMR in a subset of cases, predominantly affecting MCPyV-negative tumors. Future studies will establish whether this subset of MCC patients respond better to immune checkpoint inhibitor therapy.