Cytoplasmic/nuclear expression without mutation of exon 3 of the beta-catenin gene is frequent in the development of the neoplasm of the uterine cervix

Gynecol Oncol. 2001 Sep;82(3):450-5. doi: 10.1006/gyno.2001.6298.

Abstract

Objective: The dual function of beta-catenin (e.g., as an intermediate protein between adherence junctions and the microfilaments, and as a mediator of the Wnt signaling pathway) is currently known. Stabilization of beta-catenin and subsequent activation of the Wnt signaling pathway are involved in the development of some malignancies. We analyzed the immunohistochemical localization of beta-catenin and the somatic mutation of exon 3 of the beta-catenin gene in the malignant phenotype of the uterine cervix.

Methods: Immunohistochemical localization of beta-catenin and mutation of exon 3 of the beta-catenin gene were analyzed in 38 precancerous lesions and 43 cancerous lesions.

Results: In normal cervix, beta-catenin was observed around the plasma membrane of the cells in the basal and parabasal layers of the epithelium. The frequency of cytoplasmic/nuclear beta-catenin expression correlated with a high histological grade of cervical intraepithelial neoplasia. Among invasive carcinomas, 11 (73%) of 15 samples showed cytoplasmic/nuclear localization to variable extents. A mutational analysis showed that mutation occurred in 7 of 68 specimens. Six cases with mutations revealed cytoplasmic/nuclear beta-catenin expression, though 32 (84%) of the 38 samples showing cytoplasmic/nuclear beta-catenin expression were not associated with the mutation.

Conclusion: These results indicate that cytoplasmic/nuclear expression of beta-catenin is associated with the malignant phenotype of the cervix, but the contribution of mutation of the beta-catenin gene is limited.

MeSH terms

  • Adult
  • Aged
  • Carcinoma in Situ / genetics
  • Carcinoma in Situ / metabolism
  • Carcinoma in Situ / pathology
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Nucleus / metabolism
  • Cytoplasm / metabolism
  • Cytoskeletal Proteins / biosynthesis
  • Cytoskeletal Proteins / genetics*
  • Exons*
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Mutation*
  • Polymerase Chain Reaction
  • Precancerous Conditions / genetics*
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / pathology
  • Trans-Activators*
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology
  • beta Catenin

Substances

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