Cadherin-catenin expression in primary colorectal cancer: A survival analysis

Abstract

Both cell adhesion and cell signalling events are mediated by components of the cadherin-catenin complex. Loss of expression of the components of this complex have been shown to correlate with invasive behaviour in many tumour types although their exact role in colorectal cancer remains unclear. Immunohistochemical analysis of the expression of components of the cadherin-catenin complex in colorectal cancers from 60 patients was undertaken. Loss of memberanous expression of E-cadherin, α-catenin and β-catenin was demonstrated in 52%, 85% and 40% of tumours respectively. Focal nuclear expression of β-catenin (< 75% of cells per section), usually associated with cytoplasmic expression, was clearly demonstrated in 19 (32%) tumours while widespread nuclear expression (> 75% of tumour cells per section) was seen in 11 (18%) tumours. Loss of membranous α-catenin expression significantly correlated with tumour dedifferentiation (P = 0.009). There was a trend towards an association between advanced tumour stage and loss of membranous expression of α-catenin or β-catenin, although these associations were not statistically significant. Univariate analysis revealed that advanced Dukes' stage, tumour de-differentiation, loss of membranous β-catenin expression, cytoplasmic β-catenin expression and widespread nuclear expression of β-catenin all correlated with short survival following apparently curative resection of the primary tumour. However, only Dukes' stage (P = 0.002), tumour grade (P = 0.02) and widespread nuclear expression of β-catenin (P = 0.002) were independent predictors of short survival. Disturbed growth signalling events in colorectal tumours are thought to result in nuclear accumulation of β-catenin. Consequently, tumours with widespread nuclear expression of β-catenin are likely to have severely abnormal growth characteristics, and which therefore might be predictive of short survival in these patients.