beta-catenin expression and mutational analysis in renal cell carcinomas

Pathol Int. 2000 Sep;50(9):725-30. doi: 10.1046/j.1440-1827.2000.01111.x.


beta-Catenin acts as a downstream transcriptional activator of the Wingless-Wnt signaling pathway. The beta-catenin-Tcf complex transactivates the downstream genes that regulate cell proliferation or inhibit apoptosis. The activation of this pathway through stabilization of beta-catenin is caused either by inactivating mutations of adenomatous polyposis coli (APC) tumor suppressor gene or by activating mutations in beta-catenin exon 3. To determine whether the abnormal expression and activating mutations in exon 3 of the beta-catenin gene are implicated in renal cell carcinogenesis, 52 renal cell carcinomas (RCC) were analyzed by immunohistochemistry, polymerase chain reaction-single-strand conformational polymorphism analysis (PCR-SSCP), and direct DNA sequencing. Immunohistochemically, all cases, as well as normal kidneys, showed membranous and/or cytoplasmic staining patterns without nuclear localization. However, the cytoplasmic accumulations of beta-catenin were observed in five (22.7%) of 22 cases of conventional (clear cell) renal carcinoma, but not in papillary or chromophobe renal carcinomas. The beta-catenin mutation was identified in only one case of conventional renal carcinoma and was a single-base missense mutation on codon 61, leading to substitution of glutamine by arginine. In conclusion, this study demonstrates that beta-catenin mutations are a relatively rare event in RCC and that cytoplasmic accumulations of beta-catenin protein are found only in conventional (clear cell) renal carcinomas. These data suggest that the activation of the beta-catenin signaling pathway may partly play a role in the development of conventional RCC.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Carcinoma, Papillary / genetics
  • Carcinoma, Papillary / metabolism
  • Carcinoma, Papillary / pathology
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology
  • Cytoskeletal Proteins / biosynthesis
  • Cytoskeletal Proteins / genetics*
  • DNA Mutational Analysis
  • DNA Primers / chemistry
  • DNA, Neoplasm* / analysis
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation, Missense
  • Neoplasm Staging
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Trans-Activators*
  • beta Catenin


  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • DNA Primers
  • DNA, Neoplasm
  • Trans-Activators
  • beta Catenin