title: Expression of Mucin-1 in multiple myeloma and its precursors: correlation with glycosylation and subcellular localization.
abstract: OBJECTIVE
  Recent reports suggest a possible role for extracellular (MUC1N) and transmembrane (MUC1C) subunits of Mucin 1 (MUC1) in the pathogenesis of multiple myeloma (MM). Nuclear translocation of MUC1C is involved in activation of various oncogenic signalling pathways and both MUC1 subunits are potential therapeutic targets. We aimed at performing a comprehensive expression analysis of the MUC1 subunits in plasma cell dyscrasias.
  
  
  RESULTS
  Immunohistochemistry with monoclonal antibodies against the MUC1N subunit (EMA and 5E10) tumour-associated glycoforms of MUC1N (5E5) and the MUC1C subunit were applied to a series of biopsies from normal controls (n = 10) and plasma cell dyscrasias (n = 121). Clonal plasma cells showed reduced MUC1N expression, and the 5E5 MUC1N epitope was expressed only in neoplastic plasma cells. Nuclear localization of MUC1C was equally frequent in all disease stages and did not differ from the control cases. Loss of both MUC1 subunits in MM (n = 12) was associated with significantly shorter overall survival and was more frequent in pretreated MM samples.
  
  
  CONCLUSIONS
  Our findings indicate that aberrant glycosylation of MUC1 is an early event in the pathogenesis of MM. In contrast, MUC1C nuclear localization is not likely to be a driver of tumour progression.
authors.affiliation: Institute of Pathology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Mindaugas
authors.initials: M
authors.lastname: Andrulis
authors.forename: Elena
authors.initials: E
authors.lastname: Ellert
authors.forename: Ulla
authors.initials: U
authors.lastname: Mandel
authors.forename: Henrik
authors.initials: H
authors.lastname: Clausen
authors.forename: Nicola
authors.initials: N
authors.lastname: Lehners
authors.forename: Marc-Steffen
authors.initials: MS
authors.lastname: Raab
authors.forename: Hartmut
authors.initials: H
authors.lastname: Goldschmidt
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schwartz-Albiez
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism* / Q000473:pathology; D000939:Epitopes / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D018396:Mucin-1 / Q000378:metabolism*; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D010950:Plasma Cells / Q000378:metabolism* / Q000473:pathology; D021122:Protein Subunits / Q000378:metabolism; D013347:Subcellular Fractions
chemical_list: D000939:Epitopes; D018396:Mucin-1; D021122:Protein Subunits
keywords: MUC1 nuclear expression; glycosylation; mucin 1; multiple myeloma