Study of a High Risk Group for Liver Metastasis of Colorectal Cancer Evaluated by Molecular Biology and Immunohistochemistry Approach

Katsuyuki Kunieda, Hisashi Kohmura, Jun Sano, Kazuya Yamaguchi, Shinichiro Aoki, Fumichika Kitamura, Yasuyuki Sugiyama and Shigetoyo Saji

The Second Department of Surgery Gifu University School of Medicine

[Purpose] To facilitate identification of a high risk group of colorectal cancer patients with liver metastasis, we studied the relationship between gene products and liver metastasis by the PCR method and immunohistochemical staining. [Results] 1) Expression of MMP-9, uPA, and TIMP mRNA as assessed by RT-PCR was studied in relation to liver metastasis in 48 colorectal cancer patients. The incidence of gene expression of MMP-9 and uPA was significantly higher in cases with liver metastasis, and MMP-9 (+) and uPA (+), and MMP(+), and TIMP(-), were significantly linked to metastatic spread to the liver. 2) Immunohistochemical expression of p53, c-erbB-2, CD44, nm23, and PCNA-LI was compared in 33 cases with metachronous liver metastasis (metastasis group) and 66 cases without liver metastasis (control group), and the incidences of CD44(+), nm23(-), and PCNA-LI≥60 were found to be significantly higher in the metastasis group than in the controls. 3) Study of angiogenic factors also showed VEGF and MVD to be significantly associated with liver metastasis. 4) Detection of free cancer cells in mesenteric veinous blood draining tumors by PCR using CEA and CK-20 primers showed that the positive rates increased with clinical stage. Seven patients in the group without obvious liver metastasis were positive, and metachronous liver metastasis was observed in 2 of them. [Conclusions] MMP-9, uPA, TIMP, VEGF, PCNA, nm23, and CD44 have significant correlations with liver metastasis by colorectal cancer, and analyzing them is considered useful for identification of cases at high risk of liver metastasis along with use of the PCR method to detect free cancer cells in the mesenteric veins draining tumors.

Key words
liver metastasis of colorectal cancer, angiogenic factor, MMP-9

Reprint requests
Katsuyuki Kunieda The Second Department of Surgery, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu-city, 500-8705 JAPAN

Accepted
December 22, 1999

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