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

Objective. The dual function of β-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 β-catenin and subsequent activation of the Wnt signaling pathway are involved in the development of some malignancies. We analyzed the immunohistochemical localization of β-catenin and the somatic mutation of exon 3 of the β-catenin gene in the malignant phenotype of the uterine cervix. Methods. Immunohistochemical localization of β-catenin and mutation of exon 3 of the β-catenin gene were analyzed in 38 precancerous lesions and 43 cancerous lesions. Results. In normal cervix, β-catenin was observed around the plasma membrane of the cells in the basal and parabasal layers of the epithelium. The frequency of cytoplasmic/nuclear β-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 β-catenin expression, though 32 (84%) of the 38 samples showing cytoplasmic/nuclear β-catenin expression were not associated with the mutation. Conclusion. These results indicate that cytoplasmic/nuclear expression of β-catenin is associated with the malignant phenotype of the cervix, but the contribution of mutation of the β-catenin gene is limited.