title: Clinicopathological analysis of β-catenin and Axin-1 in solid pseudopapillary neoplasms of the pancreas.
abstract: BACKGROUND
  Solid pseudopapillary neoplasm (SPN) is a distinct pancreatic neoplasm and has characteristic, aberrant nuclear expression of β-catenin in most cases. However, alterations in components of the Wnt pathway, other than the β-catenin (CTNNB1) gene mutation, have not been identified. In this study, we investigated the status of Axin-1, the spectrum of mutations in the CTNNB1 gene, and the clinicopathological features of SPNs.
  
  
  METHODS
  We collected 27 SPNs from 25 patients. A tissue microarray was constructed to perform immunohistochemistry for β-catenin, E-cadherin, and Axin-1. The CTNNB1 and AXIN1 gene mutations were analyzed by DNA sequencing. Finally, the clinicopathological features of SPNs were analyzed for association with the CTNNB1 mutations and the Axin-1 alterations.
  
  
  RESULTS
  All 27 SPNs expressed nuclear immunoreactivity of β-catenin and exhibited a lack of membranous decoration of E-cadherin. All SPNs harbored CTNNB1 gene mutations. No alterations were present in the AXIN1 gene, and the immunohistochemical analysis revealed weak or absent reactivity of Axin-1 in the cytosol. All cases with a codon-37 CTNNB1 mutation had weak Axin-1 immunoreactivity in the cytoplasm (P = 0.018). No other significant correlation was found between clinicopathological parameters, CTNNB1 mutations, and Axin-1 alterations.
  
  
  CONCLUSIONS
  Nuclear β-catenin immunoexpression is characteristic for SPNs and corresponds to the CTNNB1 mutation. The Wnt pathway is involved in the tumorigenesis of SPNs, primarily through the alteration of β-catenin. Despite the absence of any identifiable genetic mutation, a low level of Axin-1 in the cytoplasm might contribute to the aberrant distribution of β-catenin in SPNs.
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University School of Medicine, Taoyuan, Taiwan.
authors.forename: Shih-Chiang
authors.initials: SC
authors.lastname: Huang
authors.forename: Kwai-Fong
authors.initials: KF
authors.lastname: Ng
authors.forename: Ta-Sen
authors.initials: TS
authors.lastname: Yeh
authors.forename: Hao-Cheng
authors.initials: HC
authors.lastname: Chang
authors.forename: Chia-Yi
authors.initials: CY
authors.lastname: Su
authors.forename: Tse-Ching
authors.initials: TC
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D060466:Axin Protein / Q000235:genetics* / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003062:Codon; D003600:Cytosol / Q000378:metabolism; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D052138:Genes, Neoplasm; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017354:Point Mutation; D046888:Tissue Array Analysis; D060449:Wnt Signaling Pathway; D055815:Young Adult; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: C555451:AXIN1 protein, human; D060466:Axin Protein; D015820:Cadherins; D003062:Codon; D051176:beta Catenin