title: Homo- and heterotypic cell-cell contacts in Merkel cells and Merkel cell carcinomas: heterogeneity and indications for cadherin switching.
abstract: OBJECTIVE
  Merkel cell carcinomas (MCCs) are rare but aggressive tumours associated recently with Merkel cell polyomavirus (MCV). As development and progression of several types of carcinomas can be promoted by changes in cell adhesion proteins, the aim of this study was to examine homo- and heterotypic cell contacts of Merkel cells and MCCs.
  
  
  RESULTS
  Merkel cells of healthy glabrous epidermis and 52 MCCs were analysed 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 polymerase chain reaction.
  
  
  CONCLUSIONS
  Assuming that MCCs originate from Merkel cells, our data indicate a switch from E- and P-cadherin to N-cadherin during tumorigenesis. Whether the unexpected heterogeneity of junctional proteins can be exploited for prognostic and therapeutic purposes will need to be examined.
authors.affiliation: Department of Dermatology, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Werling
authors.forename: Yvette
authors.initials: Y
authors.lastname: Doerflinger
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Brandner
authors.forename: Franca
authors.initials: F
authors.lastname: Fuchs
authors.forename: Jürgen C
authors.initials: JC
authors.lastname: Becker
authors.forename: David
authors.initials: D
authors.lastname: Schrama
authors.forename: Hjalmar
authors.initials: H
authors.lastname: Kurzen
authors.forename: Sergij
authors.initials: S
authors.lastname: Goerdt
authors.forename: Wiebke K
authors.initials: WK
authors.lastname: Peitsch
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000952:Antigens, Polyomavirus Transforming / Q000302:isolation & purification; D015820:Cadherins / Q000378:metabolism*; D036022:Capsid Proteins / Q000302:isolation & purification; D015266:Carcinoma, Merkel Cell / Q000378:metabolism / Q000648:ultrastructure* / Q000821:virology; D002448:Cell Adhesion / Q000502:physiology; D003896:Desmosomes / Q000648:ultrastructure*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D018862:Merkel Cells / Q000378:metabolism / Q000648:ultrastructure* / Q000821:virology; D018613:Microscopy, Confocal; D008875:Middle Aged; D027601:Polyomavirus Infections / Q000150:complications / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000378:metabolism / Q000648:ultrastructure* / Q000821:virology
chemical_list: D000952:Antigens, Polyomavirus Transforming; D015820:Cadherins; D036022:Capsid Proteins; C062481:VP1 protein, polyomavirus