Tissue factor expression in human colorectal carcinoma: correlation with hepatic metastasis

S. Seto, MD, H. Onodera, MD, T. Kaido, MD, A. Yoshikawa, MD, S. Ishigami, MD, S. Arii, MD, M. Imamura, MD

Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

AIM. It has been suggested that tissue factor (TF) plays an important role in tumor metastasis. Its expression in sarcoma cells was reported to up-regulates vascular endothelial growth factor (VEGF) gene and thereby enhances tumor angiogenesis, which is essential for tumor metastasis. Although many malignant tumors have been reported to express this protein constitutively, recent clinical studies have focused mainly on the correlations among TF expression, tumor progression and histological grade. Therefore, to address the role of TF and the underlying mechanism in hematogenous metastasis of colorectal carcinoma, the authors analyzed the correlations among TF expression , hepatic metastasis and VEGF gene expression in surgical specimens. Furthermore, they analyzed the prognostic significance of TF expression with respect to overall patient survival. METHODS. Expression of TF and that of VEGF gene in 67 advanced colorectal carcinoma specimens were studied immunohistochemistry and by Northern blot analysis, respectively. The relations between TF expression and hepatic metastasis and other factors were analyzed by univariate and multivariate statistics. Survival rates were calculated using the Kaplan-Meier method. RESULTS. Univariate and multivariate analysis showed TF expression to be a significant (P = 0.0001) and independent risk factor for hepatic metastasis , whereas a weak but no significant correlation was observed between TF and VEGF gene expression. The outcomes in the TF positive group were significantly worse in all cases (P = 0.0001) and in the cases without synchronous hepatic metastasis (P = 0.016). CONCLUSIONS. TF expression is a suitable indicator of both hepatic metastasis and prognosis for colorectal carcinoma patients.

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Metastasis.

This presentation received an honorable mention in our poster contest and was recognized with the Symposium Presidents' Award for Scientific Excellence.