Expression of Mucin-1 in multiple myeloma and its precursors: correlation with glycosylation and subcellular localization
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Expression of Mucin-1 in multiple myeloma and its precursors : correlation with glycosylation and subcellular localization. / Andrulis, Mindaugas; Ellert, Elena; Mandel, Ulla; Clausen, Henrik; Lehners, Nicola; Raab, Marc-Steffen; Goldschmidt, Hartmut; Schwartz-Albiez, Reinhard.
I: Histopathology, Bind 64, Nr. 6, 05.2014, s. 799-806.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Expression of Mucin-1 in multiple myeloma and its precursors
T2 - correlation with glycosylation and subcellular localization
AU - Andrulis, Mindaugas
AU - Ellert, Elena
AU - Mandel, Ulla
AU - Clausen, Henrik
AU - Lehners, Nicola
AU - Raab, Marc-Steffen
AU - Goldschmidt, Hartmut
AU - Schwartz-Albiez, Reinhard
N1 - © 2013 John Wiley & Sons Ltd.
PY - 2014/5
Y1 - 2014/5
N2 - AIMS: 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.METHODS AND 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.
AB - AIMS: 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.METHODS AND 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.
U2 - 10.1111/his.12330
DO - 10.1111/his.12330
M3 - Journal article
C2 - 24251368
VL - 64
SP - 799
EP - 806
JO - Histopathology
JF - Histopathology
SN - 0309-0167
IS - 6
ER -
ID: 119170161