Expression of the cell-cell adhesion molecule beta-catenin in colorectal carcinomas and their metastases

To study the dynamic events leading to impaired cell-cell adhesion upon transition to the invasive phenotype of colorectal cancer (CRC), we examined three distinct beta-catenin expression patterns (membranous, cytoplasmic, and nuclear) in the paired samples of the primary tumours (P) and their metastatic lesions (M). beta-catenin expression was detected by immunohistochemistry (IHC) in 33 pairs of the primary CRC and their metastases. In a pair-wise (P-M) comparison, the membranous index (MI) was significantly different between P and M (p=0.036, Wilcoxon Signed-Ranks test), while cytoplasmic index (CI) and nuclear index (NI) values did not significantly deviate between P and M. MI in primary tumours was inversely related to the patient's age (p=0.04) and tumour grade (p=0.03), while patients with low MI in M had a high rate of metastasis at diagnosis (p=0.06). CI in P was lower in patients with LN involvement (p=0.02) and in advanced tumour stage (p=0.002). Tumours of the ascending colon had the highest CI in their M (p=0.04). Interestingly, high MI of the M lesions was a significant predictor of favourable overall survival (OS) in univariate (Kaplan-Meier) survival analysis (p=0.035). In conclusion, significant aberrations in beta-catenin expression probably take place in CRC cells during the development of metastatic phenotype, but a change from membrane expression to cytoplamic and/or nuclear expression is not a prerequisite for metastasis in all cases.