Published in:
01-11-2010 | Original Article
γ-Catenin is an independent prognostic marker in early stage colorectal cancer
Published in: International Journal of Colorectal Disease | Issue 11/2010
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Purpose
Expression and role of γ-catenin in colorectal carcinogenesis is not well understood. We aimed at characterizing γ-catenin’s expression pattern during colorectal carcinogenesis.
Methods
The expression pattern of γ-catenin was characterized in adenomas, primary colorectal carcinomas, and their corresponding metastases. Since this descriptive immunohistochemical analysis revealed upregulation of γ-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 γ-catenin expression with that of β-catenin was performed.
Results
In normal colonic epithelium and adenomas, γ-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 γ-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 γ-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).
Conclusions
The correlation of upregulated cellular γ-catenin levels with higher recurrences and impaired survival suggests a tumor promoting role of γ-catenin in colorectal cancer. γ-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.