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 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.


CONCLUSIONS
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.
Shinohara
A
A
Department of Obstetrics and Gynecology, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu, 500-8705, Japan.
Yokoyama
Y
Y
Wan
X
X
Takahashi
Y
Y
Mori
Y
Y
Takami
T
T
Shimokawa
K
K
Tamaya
T
T
D000328:Adult; D000368:Aged; D002278:Carcinoma in Situ / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015534:Trans-Activators; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin