Progression of Hepatocellular Carcinoma and the Host Immune System

Michiyoshi Hisanaga, Yoshiyuki Nakajima, Mitsuo Nagao, Hiromichi Kanehiro, Yukio Aomatsu, Saiho Ko, Takatsugu Yamada and Hiroshige Nakano

Department of Surgery 1, Nara Medical University

We investigated the expression of Fas receptor (Fas) /ligand (FasL) in 47 patients with hepatocellular carcinoma (HCC). Fas and FasL expression were detected in 16 patients and 19 patients by immunohistochemistry and RT-PCR, respectively. An inverse relationship was noted between Fas and FasL expression in HCCs. In noncancerous liver tissue (n=37), Fas expression on the cell surface was upregulated in 18 cases, and FasL expression was detected in 6 cases. In the Fas-positive cases, there was more tumor cell apoptosis, and the disease-free survival rate was higher, compared with the Fas-negative cases. The soluble Fas (sFas) and soluble FasL (sFasL) levels of the HCC patients were significantly higher and lower, respectively, than in healthy volunteer. Generation of sFas was detected in the hepatocytes and tumor-infiltrating cells rather than in the hepatoma cells. These results indicate that hepatoma cells may stop expressing Fas on themselves and let the hepatocytes and tumor-infiltrating cells generate sFas to escape the host immune system and to produce metastasis. The fact that hepatocytes in the pericancerous pseudolobules expressed FasL suggests that FasL may contribute to malignant transformation and carcinogenesis.

Key words
Hepatocellular carcinoma, Fas, Fas ligand (FasL)

Reprint requests
Michiyoshi Hisanaga Department of Surgery 1, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522 JAPAN

Accepted
December 22, 1999

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