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Loss of ezrin in human intrahepatic cholangiocarcinoma is associated with ectopic expression of E‐cadherin
Author(s) -
Guedj Nathalie,
Vaquero Javier,
Clapéron Audrey,
Mergey Martine,
Chrétien Yves,
Paradis Valérie,
Fouassier Laura
Publication year - 2016
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.12931
Subject(s) - ezrin , ectopic expression , cadherin , gene silencing , cancer research , cytoplasm , biology , cell , carcinogenesis , immunohistochemistry , cell adhesion , cell adhesion molecule , catenin , pathology , microbiology and biotechnology , cancer , cell culture , medicine , cytoskeleton , immunology , signal transduction , gene , biochemistry , wnt signaling pathway , genetics
Aims Ezrin connects proteins from the plasma membrane to the subcortical cytoskeleton, and contributes to epithelial integrity by interacting with the cell–cell adhesion molecule E‐cadherin. In the liver, ezrin is restricted to cholangiocytes, where it regulates biliary secretory functions. During carcinogenesis, ezrin expression is impaired and associated with enhancement of cell migratory activity in cancer cells; therefore, we aimed to analyse ezrin in cholangiocarcinogenesis. Methods and results Ezrin expression was evaluated by immunohistochemistry on tissue microarrays from 94 surgical specimens of intrahepatic cholangiocarcinoma ( CCA ), and correlated with clinicopathological factors and E‐cadherin expression. Ezrin function was also analysed in human CCA cell lines. In CCA , ezrin was negative/weakly expressed in 49 cases (52%) and moderately/strongly expressed in 45 cases (48%), mostly in cell cytoplasm. The negative/weak expression of ezrin was more frequent in peripheral than in perihilar CCA ( P = 0.002), and was associated with high tumour size ( P = 0.001), low mucus secretion ( P = 0.042), the presence of satellite nodules ( P = 0.024), and ectopic cytoplasmic expression of E‐cadherin ( P = 0.005). In vitro , silencing of ezrin in CCA cells caused internalization of E‐cadherin and favoured cell migration. Conclusions Ezrin is down‐regulated during cholangiocarcinogenesis, and its loss results in a more aggressive phenotype.