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Expression of Thrombospondin-1 in Resected Colorectal Liver Metastases Predicts Poor Prognosis

Authors' Affiliations: Departments of ¹ Surgery, ² Oncology, ³ Pathology, University Hospitals of Leicester, Leicester, United Kingdom and ⁴ Department of Surgery, Royal Liverpool Hospital, Liverpool, United Kingdom

Requests for reprints: Christopher D. Sutton, Department of Hepatobiliary Surgery, Leicester Royal Infirmary, Infirmary Square, Leicester, LE1 5WW, United Kingdom. Phone: 441-162-700382; Fax: 116-258-5631; E-mail: crisdsutton{at}hotmail.com.

Purpose: The aim of this study was to examine the expression and prognostic relevance of thrombospondin-1 (TSP-1) in tumor biopsies taken from a consecutive series of liver resections done at the University Hospitals of Leicester and the Royal Liverpool Hospital.

Experimental Design: Patients having undergone a liver resection for colorectal liver metastases at our institutions between 1993 and 1999 inclusive were eligible. Inclusion criteria were curative intent, sufficient tumor biopsy, and patient follow-up data. One hundred eighty-two patients were considered in this study. Standard immunohistochemical techniques were used to study the expression of TSP-1 in 5-µm tumor sections from paraffin-embedded tissue blocks. TSP-1 was correlated with survival using the Kaplan-Meier method and log-rank test for univariate analysis and the Cox proportional hazard model for multivariate analysis.

Results: One hundred eighty-two patients (male, n = 122 and female, n = 60) ages between 25 and 81 years (mean, 61 years) were included. TSP-1 was expressed around blood vessels (n = 45, 25%) or in the stroma (n = 59, 33%). No expression was detected in the remaining tumors. TSP-1 significantly correlated with poor survival on univariate (P = 0.01 for perivascular expression and P = 0.03 for stromal expression) and multivariate analysis (P = 0.01 for perivascular expression).

Conclusion: TSP-1 is a negatively prognostic factor for survival in resected colorectal liver metastases.