γ-Catenin is an independent prognostic marker in early stage colorectal cancer

Expression and role of gamma-catenin in colorectal carcinogenesis is not well understood. We aimed at characterizing gamma-catenin's expression pattern during colorectal carcinogenesis. The expression pattern of gamma-catenin was characterized in adenomas, primary colorectal carcinomas, and their corresponding metastases. Since this descriptive immunohistochemical analysis revealed upregulation of gamma-catenin in the invasive front of both primary tumors and metastases, a tissue microarray (TMA) was performed, allowing for correlation of subcellular expression patterns with disease recurrence and cancer-specific survival. Comparison of gamma-catenin expression with that of beta-catenin was performed. In normal colonic epithelium and adenomas, gamma-catenin was weakly expressed at the membrane. In central areas of primary colorectal carcinomas, membranous and cytoplasmatic expression was present, with cytoplasmatic and nuclear upregulation of gamma-catenin in the invasive fronts. Expression patterns found in metastases resembled those of their respective primary tumors. Subsequent TMA analysis showed that upregulation of cytoplasmatic gamma-catenin in the invasive fronts of curatively resected early T2 and T3 colorectal carcinomas was associated with shortened disease-free survival and an increased risk of death (p = 0.003; hazard ratio = 2.98; 95% confidence interval, 1.44-6.18). The correlation of upregulated cellular gamma-catenin levels with higher recurrences and impaired survival suggests a tumor promoting role of gamma-catenin in colorectal cancer. gamma-Catenin may therefore serve as a marker for identifying patients who are at increased risk of disease recurrence who may benefit from closer follow-up and adjuvant therapy.