Expression of MUC 1 and Ep-CAM in Merkel cell carcinomas: implications for immunotherapy.
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.
Kurzen
Hjalmar
H
Department of Dermatology, University of Heidelberg, Vossstrasse 2, 69115 Heidelberg, Germany.
Kaul
Sepp
S
Egner
Ursel
U
Deichmann
Martin
M
Hartschuh
Wolfgang
W
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015266:Carcinoma, Merkel Cell / Q000737:chemistry* / Q000473:pathology* / Q000556:secondary; D015815:Cell Adhesion Molecules / Q000032:analysis*; D000071858:Epithelial Cell Adhesion Molecule; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000032:analysis*; D020539:Sequence Analysis, Protein; D012878:Skin Neoplasms / Q000737:chemistry* / Q000473:pathology* / Q000556:secondary
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D008565:Membrane Proteins