Homo- and heterotypic cell-cell contacts in Merkel cells and Merkel cell carcinomas: surprising heterogeneity and indications for cadherin switching

Anna Maria Werling (1, 2) , Yvette Doerflinger (1, 2) , Johanna M. Brandner (3) , Franca Fuchs (3) , Jürgen C. Becker (4) , David Schrama (4) , Hjalmar Kurzen (1, 5) , Sergij Goerdt (1) , Wiebke Katharina Peitsch (6)

1 Department of Dermatology
2 Helmholtz Group for Cell Biology
3 Department of Dermatology
4 Department of Dermatology
5 Dermatological Practice
6 Department of Dermatology

Aims: Merkel cell carcinomas (MCCs) are rare but aggressive tumours recently associated with Merkel cell polyomavirus (MCV). As development and progression of several types of carcinomas can be promoted by changes in cell adhesion proteins, we have examined homo- and heterotypic cell contacts of Merkel cells and MCCs. Methods and Results: Merkel cells of healthy glabrous epidermis and 52 MCCs were analyzed by double-label immunostaining, immunofluorescence and confocal microscopy. Merkel cells were connected to keratinocytes by E- and P-cadherin, desmoglein 2 and desmocollin 2. In contrast, the vast majority of MCCs (90%) contained N-cadherin but only 67 and 65% contained E- and P-cadherin, respectively. Interestingly, P-cadherin was absent significantly more frequently in lymph node metastases than in primary tumours and by trend in more advanced clinical stages. Moreover, major subsets of MCCs synthesized desmoglein 2 and, surprisingly, tight junction proteins. No significant differences were observed upon stratification for MCV DNA, detected in 84% of tumours by real-time PCR. Conclusions: Assuming that MCCs originate from Merkel cells, our data indicate a switch from E- and P-cadherin to N-cadherin during tumourigenesis. Whether the unexpected heterogeneity of junctional proteins can be exploited for prognostic and therapeutic purposes will have to be examined.

Mots clés: Medicine

Anna Maria Werling, Yvette Doerflinger, Johanna M. Brandner, Franca Fuchs, Jürgen C. Becker, et al.. Homo- and heterotypic cell-cell contacts in Merkel cells and Merkel cell carcinomas: surprising heterogeneity and indications for cadherin switching. Histopathology, 2011, 58 (2), pp.286. ⟨10.1111/j.1365-2559.2011.03748.x⟩. ⟨hal-00614749⟩