title: High expression of tumour-associated trypsin inhibitor correlates with liver metastasis and poor prognosis in colorectal cancer.
abstract: 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 (>50% 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.
authors.affiliation: Department of Laboratory Medicine, Center for Molecular Pathology, Malmö University Hospital, Lund University, Malmö, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Gaber
authors.forename: M
authors.initials: M
authors.lastname: Johansson
authors.forename: U-H
authors.initials: UH
authors.lastname: Stenman
authors.forename: K
authors.initials: K
authors.lastname: Hotakainen
authors.forename: F
authors.initials: F
authors.lastname: Pontén
authors.forename: B
authors.initials: B
authors.lastname: Glimelius
authors.forename: A
authors.initials: A
authors.lastname: Bjartell
authors.forename: K
authors.initials: K
authors.lastname: Jirström
authors.forename: H
authors.initials: H
authors.lastname: Birgisson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012008:Recurrence; D016019:Survival Analysis; D046888:Tissue Array Analysis; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D014359:Trypsin Inhibitor, Kazal Pancreatic