Predictive value of nuclear betacatenin expression for the occurrence of distant metastases in rectal cancer
| Autor: | Wolfgang G. Ballhausen, Otto Dworak, Marc A. Reymond, Andreas Jung, T. Kirchner, Cornelia Kraus, Klaus Günther, Thomas Brabletz, Werner Hohenberger, Ferdinand Köckerling |
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| Rok vydání: | 1998 |
| Předmět: |
Male
Pathology medicine.medical_specialty Colorectal cancer Gene Expression Adenocarcinoma Disease-Free Survival Metastasis Predictive Value of Tests Biomarkers Tumor medicine Carcinoma Humans Nuclear protein beta Catenin Tumor marker Oncogene Rectal Neoplasms business.industry Gastroenterology Nuclear Proteins DNA Neoplasm Sequence Analysis DNA General Medicine Middle Aged Cadherins Prognosis medicine.disease Cytoskeletal Proteins Trans-Activators Immunohistochemistry Female business |
| Zdroj: | Diseases of the Colon & Rectum. 41:1256-1261 |
| ISSN: | 0012-3706 |
| DOI: | 10.1007/bf02258226 |
| Popis: | PURPOSE: Adenomatous polyposis coli protein, glycogen synthetase kinase-3-beta, T cell transcription factor/lymphoid enhancer-binding factor, and beta-catenin modulate cell differentiation and proliferation via the expression of effector genes. It has recently been postulated that betacatenin is a potent oncogene of sporadic colorectal carcinogenesis and a prognostic tumor marker. Our aim was to investigate whether the nuclear overexpression of betacatenin, possibly caused by mutations in exon 3 of betacatenin (CTNNB1), is correlated with distant metastatic spread or disease-free survival in rectal carcinoma. METHODS: Immunohistochemical analysis was performed with an anti-beta-catenin-monoclonal antibody on paraffin sections of two groups of patients (n=2 × 77) with rectal carcinoma curatively treated by surgery alone. The patients selected were all free of local disease, to exclude surgical influence. Patient groups were matched for age, gender, International Union Against Cancer stage, and year of operation (1982 to 1991) and differed only in subsequent metachronous distant metastatic spread. Follow-up was prospective (median, 9.6 years). Three staining patterns were defined: membranous (normal), diffuse cytoplasmic (pathologic), and intense nuclear staining (pathologic). When intense nuclear staining was defined, the specimen was microdissected. Then, DNA was isolated, polymerase chain reaction-amplified, and sequenced to detect mutations in exon 3. RESULTS: Nuclear overexpression of beta-catenin correlated neither with distant metastatic spread (chisquared, 0.37;P=0.79) nor with disease-free survival (log-rank with trend,P=0.62). No mutations were found in the area of the serine/threonine-kinase glycogen synthetase kinase-3-beta-phosphorylation site in exon 3 (CTNNB1) of beta-catenin. CONCLUSION: Although beta-catenin seems to play an important role in early colorectal carcinogenesis, its value as a prognostic marker is questionable. It must be assumed that metastatic ability is determined by other factors than the disturbance of the beta-catenin T cell transcription factor/lymphoid enhancer-binding factor cascade and that other mechanisms might cause the observed nuclear translocation of beta-catenin. |
| Databáze: | OpenAIRE |
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