273 Site of intracellular expression of beta-catenin influences the outcome in sporadic colorectal cancer

Background: Stabilisation and nuclear translocation of beta-catenin are suggested to be the early events in the colorectal carcinogenesis. Nuclear accumulation of beta-catenin was associated with high-grade tumour and increased cell proliferation in epithelial cancers. The aim of our study was to correlate the effects of nuclear and cytoplasmic beta-catenin expression in patients with sporadic colorectal cancer cases with clinical outcome. Method: lmmunohistochemistry was performed on 161 histologically proven colorectal cancer cases and were assessed quantitatively. Results: Out of 161 samples, 139(86.34%) had over expressed beta- catenin either in the nucleus 54(33.54%), cytoplasm 50(31.06%) or both 35(21.74%). Nuclear expression of beta-catenin was significantly associated with well-differentiated tumours (OR=3.14 p=O.O15 Cl= 1.25-7.87) and early T’ stage disease (OR=277 p=O.O17 Cl= 1.20-6.43). Strong cytoplasmic expression was significantly associated with nodal involvement (p=O.O54 x2 test), liver metastasis (p=O.O50 x2 test) and a non-significant association with metastasis (p=O.O8 x2 test). Using Cox’s proportional hazard model, we found significant association between strong cytoplasmic expression and advanced Dukes stage disease with reduced survival (HR=1.59 p=O.O44 Cl= 1.Ol-2.50). Those with beta-catenin in the nucleus as well as cytoplasm did not show any significant association with clinical parameters. There were no significant associations found between age and overexpression. Conclusion: We demonstrate for the first time, cytoplasmic expression was associated with poor clinical outcome in colorectal cancer whereas nuclear expression had an opposite effect. These data suggest that the site of expression has a significant impact on disease progression by acting via different pathways.