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

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. (C) 2001 Academic Press.