Serum levels of type IV collagen 7S and procollagen type III N-terminal propeptide in colorectal cancer patients with hepatic metastases

Background: A variety of liver diseases accompany significant elevation of both type IV collagen 7S (IVc-7S) and procollagen type III N-terminal propeptide (P-III-P), suggesting the presence of liver fibrosis. We investigated whether metastatic liver tumors from colorectal carcinoma cause hepatic fibrosis at metastatic sites, and if serum levels of collagen precursors would suggest fibrous changes of metastatic liver tumors. Methods: Peripheral venous blood was taken from 42 patients with colorectal carcinoma, before surgery or cancer chemotherapy. A commercially available PIA kit was used to measure IV-c-7S and P-III-P in sera, and immunohistochemical staining of type IV collagen expressed at hepatic metastatic lesions was performed in 15 patients with liver metastasis. Results: Serum levels of both IV-c-7S and P-III-P correlated with the presence of hepatic metastasis. There were, however, no significant correlations between the serum levels of those molecules and either Dukes' stage, histologic differentiation, lymph node metastasis, lung metastasis, peritoneal dissemination, or depth of colorectal wall invasion. There were significant correlations between serum levels of both IV-c-7S and P-III-P and those of carcinoembryonic antigen. Serum levels of both IV-c-7S and PIII-P in the patients with multiple metastases were significantly higher than those in patients with no, or solitary, hepatic metastases. The immunohistochemical staining showed that type IV collagen was expressed at hepatic metastatic sites. Conclusion: Metastatic liver tumors from colorectal cancer form liver fibrosis at metastatic sites, and accelerate the biosynthesis of type IV and type III collagen.