The Intratumoral Distribution of Nuclear β-Catenin Is a Prognostic Marker in Colon Cancer

BACKGROUND: Most colon cancers have harbored mutations of APC or beta-catenin, both of which may lead to nuclear beta-catenin accumulation in the the tumor cells and constitutively activated expression of its target genes. In many colon cancers, however, nuclear beta-catenin accumalation were heterogeneous throughout the tumor and often confined to the tumor margin. However, the authors investigated whether the intratumoral distribution of nuclear beta-catenin can serve as a prognostic marker for survival and tumor progression of stage IIA colon cancer patients. METHODS: In total, 142 patients with primarily resected, moderately differentiated stage IIA colon cancer were included in this study. The patterning of nuclear beta-catenin expression was evaluated on immunohistochemically stained whole tissue sections of the tumors and was correlated with cancer-specific survival and disease-free survival using univariate and multivariate statistical analyses. RESULTS: Four distinct patterns of nuclear beta-catenin expression were identified, and 2 main categories comprising tumors with or without intratumoral regulation of nuclear beta-catenin were distinguished. Moreover, the results demonstrated that the patterning, and especially the regulation or absence of regulation of nuclear beta-catenin expression, was a strong predictive marker of patient survival and tumor progression. CONCLUSIONS: The current results indicated that the distribution of nuclear beta-catenin expression can be used as a good prognostic marker in patients with stage IIA colon cancer. Thus, the evaluation of nuclear beta-catenin may help to identify patients who will have a shorter than average survival and patients with a greater risk of disease progression who may be considered for adjuvant therapeutic modalities and intensified clinical aftercare in the future. Cancer 2009;115:2063-70. (c) 2009 American Cancer Society.