PMID- 26791814 OWN - NLM STAT- MEDLINE DCOM- 20171019 LR - 20181202 IS - 1365-2559 (Electronic) IS - 0309-0167 (Linking) VI - 69 IP - 2 DP - 2016 Aug TI - Loss of ezrin in human intrahepatic cholangiocarcinoma is associated with ectopic expression of E-cadherin. PG - 211-21 LID - 10.1111/his.12931 [doi] AB - 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. CI - (c) 2016 John Wiley & Sons Ltd. FAU - Guedj, Nathalie AU - Guedj N AD - Service d'anatomie pathologique Hopital Beaujon, Clichy, France. AD - INSERM, UMR 1149, Centre de Recherche sur l'Inflammation, Paris, France. FAU - Vaquero, Javier AU - Vaquero J AD - INSERM, UMR_S 938, Paris, France. AD - Sorbonne Universites, UPMC Universite Paris 06, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France. FAU - Claperon, Audrey AU - Claperon A AD - INSERM, UMR_S 938, Paris, France. AD - Sorbonne Universites, UPMC Universite Paris 06, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France. FAU - Mergey, Martine AU - Mergey M AD - INSERM, UMR_S 938, Paris, France. AD - Sorbonne Universites, UPMC Universite Paris 06, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France. FAU - Chretien, Yves AU - Chretien Y AD - INSERM, UMR_S 938, Paris, France. AD - Sorbonne Universites, UPMC Universite Paris 06, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France. FAU - Paradis, Valerie AU - Paradis V AD - Service d'anatomie pathologique Hopital Beaujon, Clichy, France. AD - INSERM, UMR 1149, Centre de Recherche sur l'Inflammation, Paris, France. FAU - Fouassier, Laura AU - Fouassier L AD - INSERM, UMR_S 938, Paris, France. AD - Sorbonne Universites, UPMC Universite Paris 06, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France. LA - eng PT - Journal Article DEP - 20160301 PL - England TA - Histopathology JT - Histopathology JID - 7704136 RN - 0 (Antigens, CD) RN - 0 (Biomarkers, Tumor) RN - 0 (CDH1 protein, human) RN - 0 (Cadherins) RN - 0 (Cytoskeletal Proteins) RN - 0 (ezrin) SB - IM MH - Aged MH - Antigens, CD MH - Bile Duct Neoplasms/diagnosis/*metabolism/pathology/surgery MH - Biomarkers, Tumor/*metabolism MH - Cadherins/*metabolism MH - Carcinogenesis MH - Cell Line, Tumor MH - Cell Membrane/metabolism MH - Cell Movement MH - Cholangiocarcinoma/diagnosis/*metabolism/pathology/surgery MH - Cytoskeletal Proteins/*metabolism MH - Down-Regulation MH - Ectopic Gene Expression MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Immunohistochemistry MH - Liver/metabolism/pathology MH - Liver Neoplasms/diagnosis/*metabolism/pathology/surgery MH - Tissue Array Analysis OTO - NOTNLM OT - E-cadherin OT - cellular biology OT - cholangiocarcinoma OT - ezrin OT - immunohistochemistry EDAT- 2016/01/23 06:00 MHDA- 2017/10/20 06:00 CRDT- 2016/01/22 06:00 PHST- 2015/04/17 00:00 [received] PHST- 2016/01/14 00:00 [accepted] PHST- 2016/01/22 06:00 [entrez] PHST- 2016/01/23 06:00 [pubmed] PHST- 2017/10/20 06:00 [medline] AID - 10.1111/his.12931 [doi] PST - ppublish SO - Histopathology. 2016 Aug;69(2):211-21. doi: 10.1111/his.12931. Epub 2016 Mar 1.