Impaired E-cadherin expression and glutamine synthetase overexpression in solid pseudopapillary neoplasm of the pancreas.
OBJECTIVE
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.
Audard
Virginie
V
Institut Cochin, Université Paris Descartes, CNRS, Paris, France.
Cavard
Catherine
C
Richa
Hubert
H
Infante
Muriel
M
Couvelard
Anne
A
Sauvanet
Alain
A
Terris
Benoît
B
Paye
François
F
Flejou
Jean-François
JF
D000328:Adult; D015820:Cadherins / Q000032:analysis / Q000235:genetics*; D021441:Carcinoma, Pancreatic Ductal / Q000737:chemistry / Q000235:genetics; D002462:Cell Membrane / Q000737:chemistry; D019938:Cyclin D1 / Q000235:genetics; D003593:Cytoplasm / Q000737:chemistry; D004252:DNA Mutational Analysis; D005260:Female; D015870:Gene Expression; D005974:Glutamate-Ammonia Ligase / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051153:Wnt Proteins / Q000502:physiology; D051176:beta Catenin / Q000032:analysis / Q000502:physiology
D015820:Cadherins; D051153:Wnt Proteins; D051176:beta Catenin; D019938:Cyclin D1; D005974:Glutamate-Ammonia Ligase