Author(s): Suzuki H, Masuda N, Shimura T, Araki K, Kobayashi T, Tsutsumi S
Beta-catenin is a component of the Wingless/Wnt signaling pathway and can activate target genes associated with proliferation and invasion, linking with the APC gene. The purpose of this study was to investigate whether nuclear expression of beta-catenin in cells at the invasive front or in the vessels was associated with liver metastasis in human colon cancer. PATIENTS AND METHODS: One hundred and eighteen patients with colorectal carcinoma who underwent surgical resection (45 patients with liver metastasis and 73 patients without liver metastasis at least 5 years after surgery) were included in the study. Proliferative activity was determined in several areas (tumor center, invasive front and in the vessels) by immunohistochemistry and whether it was correlated with liver metastasis was examined. RESULTS: In 73.1% of primary tumors, positive staining for beta-catenin was detected in the membranes at the tumor center and in the nuclei at the invasive front. In 32 patients (26.9% of all cases), beta-catenin was expressed exclusively in the nuclei of the carcinoma cells throughout the tumors. Significant differences in expression of nuclear beta-catenin in the primary tumors were detected between the liver metastasis and non-liver metastasis groups at the tumor center (p=0.004), invasive front (p=0.021) and in the vessels (p<0.0001). CONCLUSION: Nuclear accumulation of beta-catenin in cellular cells at the invasive front and in the vessels was the most powerful predictor of liver metastasis in colorectal cancer. This may be an important marker in the selection of patients for adjuvant therapy or other treatment modalities.