High expression of tumour-associated trypsin inhibitor correlates with liver metastasis and poor prognosis in colorectal cancer

Increased expression of tumour-associated trypsin inhibitor (TATI) in tumour tissue and/or serum has been associated with poor survival in various cancer forms. Moreover, a proinvasive function of TATI has been shown in colon cancer cell lines. In this study, we have examined the prognostic significance of tumour-specific TATI expression in colorectal cancer, assessed by immunohistochemistry (IHC) on tissue microarrays (TMAs) with tumour specimens from two independent patient cohorts. Kaplan-Meier analysis and Cox proportional hazards modelling were used to estimate time to recurrence, disease-free survival and overall survival. In both cohorts, a high (450% of tumour cells) TATI expression was an independent predictor of a significantly shorter overall survival. In cohort II, in multivariate analysis including age, gender, disease stage, differentiation grade, vascular invasion and carcinoembryonal antigen (CEA), high TATI expression was associated with a significantly decreased overall survival (HR = 1.82; 95% CI = 1.19-2.79) and disease-free survival (HR = 1.56; 95% CI = 1.05-2.32) in curatively treated patients. Moreover, there was an increased risk for liver metastasis in both cohorts that remained significant in multivariate analysis in cohort II (HR = 2.85; 95% CI = 1.43-5.66). In conclusion, high TATI expression is associated with liver metastasis and is an independent predictor of poor prognosis in patients with colorectal cancer. British Journal of Cancer (2009) 100, 1540-1548. doi: 10.1038/sj.bjc.6605047 www.bjcancer.com Published online 21 April 2009 (C) 2009 Cancer Research UK