Impaired E-cadherin expression and glutamine synthetase overexpression in solid pseudopapillary neoplasm of the pancreas

被引:42
作者
Audard, Virginie [3 ,4 ]
Cavard, Catherine [3 ,4 ]
Richa, Hubert [5 ]
Infante, Muriel [6 ]
Couvelard, Anne [7 ]
Sauvanet, Alain [8 ]
Terris, Benoit [1 ,4 ,9 ]
Paye, Francois [2 ]
Flejou, Jean-Francois [7 ]
机构
[1] Hop Cochin, Serv Anat Pathol, AP HP, Dept Pathol, F-75679 Paris 14, France
[2] Hop St Antoine, AP HP, Dept Digest Surg, F-75571 Paris, France
[3] Univ Paris 05, CNRS, Inst Cochin, Paris, France
[4] INSERM, Paris, France
[5] Hop Conception, AP HM, Dept Surg & Liver Transplantat, Marseille, France
[6] Hop St Antoine, Dept Pathol, F-75571 Paris, France
[7] Hop Beaujon, AP HP, Dept Pathol, Clichy, France
[8] Hop Beaujon, AP HP, Dept Digest Surg, Clichy, France
[9] Univ Paris 05, Fac Med Rene Descartes, Paris, France
关键词
solid pseudopapillary neoplasm of the pancreas; beta-catenin; E-cadherin; glutamine synthetase;
D O I
10.1097/mpa.0b013e318137a9da
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Objectives: To analyze in solid pseudopapillary neoplasm of the pancreas (SPNP) the consequences of the deregulated Wnt pathway by studying the expression of Wnt target glutamine synthetase (GLUL), cyclin D1, and E-cadherin, which is one of the beta-catenin binding partner in cell adhesion. Methods: The expression of cyclin D1 and GLUL was studied at the protein and/or messenger RNA levels, and the immunolocalization for E-cadherin was analyzed in 28 SPNPs screened for beta-catenin mutations. Expression of cyclin D1, GLUL, and beta-catenin was also assessed in pancreatic endocrine tumors as controls. Results: Cytosolic and/or nuclear accumulation of beta-catenin was observed in all tumors; an activating beta-catenin mutation was identified in 21 (91%) of 23 tumors analyzed. E-cadherin expression is lost from the membrane and is observed in intracytosolic "dotlike" structures. Whereas cyclin D1 expression is observed widely in SPNP and endocrine tumors, GLUL expression is restricted to SPNP (100%) and rare endocrine tumors (10%) displaying Wnt activation. Conclusions: The activation of the Wnt/beta-catenin pathway in SPNP has 2 main consequences. First, E-cadherin expression moved from membranous to intracytoplasmic localization. Second, GLUL expression is highly correlated with Wnt/beta-catenin activation, demonstrating its faithfulness as a Wnt target gene.
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收藏
页码:80 / 83
页数:4
相关论文
共 23 条
[1]   Solid-pseudopapillary tumors of the pancreas are genetically distinct from pancreatic ductal adenocarcinomas and almost always harbor β-catenin mutations [J].
Abraham, SC ;
Klimstra, DS ;
Wilentz, RE ;
Yeo, CJ ;
Conlon, K ;
Brennan, M ;
Cameron, JL ;
Wu, TT ;
Hruban, RH .
AMERICAN JOURNAL OF PATHOLOGY, 2002, 160 (04) :1361-1369
[2]   The ins and outs of E-cadherin trafficking [J].
Bryant, DM ;
Stow, JL .
TRENDS IN CELL BIOLOGY, 2004, 14 (08) :427-434
[3]   New targets of β-catenin signaling in the liver are involved in the glutamine metabolism [J].
Cadoret, A ;
Ovejero, C ;
Terris, B ;
Souil, E ;
Lévy, L ;
Lamers, WH ;
Kitajewski, J ;
Kahn, A ;
Perret, C .
ONCOGENE, 2002, 21 (54) :8293-8301
[4]  
de La Coste A, 1998, P NATL ACAD SCI USA, V95, P8847
[5]   Analysis of β-catenin gene mutations in pancreatic tumors [J].
Gerdes, B ;
Ramaswamy, A ;
Simon, B ;
Pietsch, T ;
Bastian, D ;
Kersting, M ;
Moll, R ;
Bartsch, D .
DIGESTION, 1999, 60 (06) :544-548
[6]   Expression of β-catenin in gastroenteropancreatic endocrine tumours:: a study of 229 cases [J].
Hervieu, V. ;
Lepinasse, F. ;
Gouysse, G. ;
Guillaud, O. ;
Barel, C. ;
Chambonniere, M-L ;
Bringuier, P-P ;
Poncet, G. ;
Lombard-Bohas, C. ;
Partensky, C. ;
Chayvialle, J-A ;
Scoazec, J-Y .
JOURNAL OF CLINICAL PATHOLOGY, 2006, 59 (12) :1300-1304
[7]   Inactivation of the E-cadherin-mediated cell adhesion system in human cancers [J].
Hirohashi, S .
AMERICAN JOURNAL OF PATHOLOGY, 1998, 153 (02) :333-339
[8]   Endocytosis of E-cadherin regulated by Rac and Cdc42 small G proteins through IQGAP1 and actin filaments [J].
Izumi, G ;
Sakisaka, T ;
Baba, T ;
Tanaka, S ;
Morimoto, K ;
Takai, Y .
JOURNAL OF CELL BIOLOGY, 2004, 166 (02) :237-248
[9]  
Karayiannakis AJ, 1998, ANTICANCER RES, V18, P4177
[10]   Solid-pseudopapillary tumor of the pancreas:: its origin revisited [J].
Kosmahl, M ;
Seada, LS ;
Jänig, U ;
Harms, D ;
Klöppel, G .
VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY, 2000, 436 (05) :473-480