Oncogenic beta-catenin and MMP-7 (matrilysin) cosegregate in late-stage clinical colon cancer. |
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Authors: | Andrei V Ougolkov Kaname Yamashita Masayoshi Mai Toshinari Minamoto |
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Institution: | Division of Diagnostic Molecular Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan. |
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Abstract: | BACKGROUND & AIMS: Recent in vitro studies showed that beta-catenin translocated into the tumor cell nucleus functions as an oncogene by transactivating oncogenes, including MMP-7. We conducted a large-scale analysis of beta-catenin and MMP-7 expression in human colon cancer to determine the potential clinical importance of these molecules. METHODS: In 202 colon cancer patients with known postoperative outcomes, we determined the expression of beta-catenin and MMP-7 in the tumors immunohistochemically and correlated the findings with the patients' clinicopathological characteristics and survival. RESULTS: We found 2 distinct patterns of beta-catenin nuclear accumulation (NA) in the colon cancers: diffuse NA (NAd) in 89 cases (44%) and selective NA at the invasion front (NAinv) in 18 cases (9%). The presence of the NAinv pattern was significantly correlated with advanced Dukes' stage (P = 0.0187) and tumor recurrence (P = 0.0005) as well as with MMP-7 expression in the tumor invasion front (P = 0.0025), resulting in extremely unfavorable clinical outcomes. A multivariate analysis determined that the NAinv expression pattern and Dukes' C stage were independent prognostic factors. CONCLUSIONS: Oncogenic activation of beta-catenin in the tumor invasion front, as represented by its NAinv pattern of expression, may be an independent and reliable indicator of membership in a subset of colon cancer patients who are highly susceptible to tumor recurrence and have a less favorable survival rate. |
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Keywords: | DFS disease-free survival GSK3β glycogen synthase kinase 3β MMP matrix metalloproteinase NA nuclear accumulation NAd diffuse nuclear accumulation NAinv nuclear accumulation in the tumor invasion front OAS overall survival PCR polymerase chain reaction RFLP restriction fragment length polymorphism TGF transforming growth factor |
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