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The Role of Gelatinase in Hepatic Metastasis of Colorectal Cancer

Department of Surgery [Y-W. T., P-H. L., R-H. H., K-J. C.], and Pathology [S-M. H.], National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan 10002, Republic of China

Purpose: To determine the role of gelatinase in the hepatic metastatic process of colorectal cancer, we correlated gelatinolytic activity in colorectal tumor tissue both to the presence of intravasated colorectal epithelial cells and to the formation of liver metastasis.

Experimental Design: The gelatinolytic activity was analyzed in tumor tissue samples from 68 colorectal cancer patients by using gelatin substrate zymography. The presence of intravasated colorectal epithelial cells was defined as detection of guanylyl cyclase C mRNA in blood sampled from drainage vein of a tumor-bearing colorectal segment.

Results: Forty of 68 patients were noted to have guanylyl cyclase C mRNA expression in their drainage venous blood. Fifteen patients were noted to have liver metastasis at the time of surgery, and another 15 patients developed liver metastasis during median follow-up period of 53 months. Either individual or total gelatinolytic activity in colorectal tumor tissue failed to predict the presence of intravasated colorectal epithelial cells in the drainage venous blood or formation of liver metastasis. Presence of both intravasated colorectal epithelial cells and high total gelatinolytic activity in colorectal tumor tissue, however, is a strong predictor of liver metastasis (P = 0.004).

Conclusion: Our data suggested that gelatinolytic activity in colorectal tumor tissues may facilitate the hepatic metastatic process in the steps after intravasation but not during or before intravasation.