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Expression of MUC 1 and Ep-CAM in Merkel cell carcinomas: implications for immunotherapy

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Abstract

The Merkel cell carcinoma (MCC) is a highly malignant carcinoma of the skin that is characterized by granules containing neuroendocrine peptides and by the expression of simple epithelial type cytokeratins. The glycoprotein Ep-CAM is a homophilic cell-cell adhesion molecule, present in most simple, pseudostratified and transitional epithelia and the tumors derived therefrom. MUC 1 is a well-established marker for squamous cell carcinomas and is generally secreted by glandular epithelial cells. We compared the expression of Ep-CAM and MUC 1 in Merkel cells and 33 cases of MCC and 12 MCC metastases using immunohistochemistry on paraffin-embedded sections. In addition, we examined the glycosylation status of MUC 1 with specific monoclonal antibodies. MUC 1 and Ep-CAM were expressed in Merkel cells and in about 82% and 70% of all MCC irrespective of clinical outcome. Both antigens were expressed in 66% of metastases. Similar to breast cancer, the presence of MUC 1 was not correlated with clinical outcome, but the staining intensity of monoclonal antibodies against glycosylation-independent and hypoglycosylated epitopes was. In MCC we found an altered glycosylation pattern in the immunodominant APDTR region of MUC 1 as compared to normal Merkel cells. Hyperglycosylated MUC 1 epitopes were not present in either MCC or normal Merkel cells. There was no correlation between glycosylation pattern and clinical outcome. Ep-CAM expression seemed to be stronger in primary MCC that metastasized than in those that did not. In conclusion, Merkel cells and the majority of MCC express Ep-CAM and MUC 1. This opens the door for treatments based on monoclonal antibodies or vaccination strategies against these antigens, already established for other tumor entities.

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Authors and Affiliations

  1. Department of Dermatology, University of Heidelberg, Voßstr.2, 69115, Heidelberg, Germany

    Hjalmar Kurzen, Ursel Egner, Martin Deichmann & Wolfgang Hartschuh

  2. Department of Gynecological Oncology, University of Heidelberg, Heidelberg, Germany

    Sepp Kaul

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  1. Hjalmar Kurzen
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  5. Wolfgang Hartschuh
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Kurzen, H., Kaul, S., Egner, U. et al. Expression of MUC 1 and Ep-CAM in Merkel cell carcinomas: implications for immunotherapy. Arch Dermatol Res 295, 146–154 (2003). https://doi.org/10.1007/s00403-003-0410-y

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  • DOI: https://doi.org/10.1007/s00403-003-0410-y

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