Analysis of multicentric carcinogenesis of HCC patients from immunological view points

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Hepatocellular carcinomas (HCC) often recur after curative resection. Recurrence in the remnant liver originates from intrahepatic metastasis (IM) from the primary resected tumor, and/or from multicentric (MC) occurrence. In order to achieve better survival after intrahepatic recurrence in HCC patients, we have surgically treated patients according to the recurrence pattern. Survival after the repeat operation was significantly better in the MC group than in the IM group (P 0.0016). Moreover, there was no significant difference between survival in the MC group after a repeat operation and survival in control patients after an initial hepatectomy. These results indicated that patients with resectable or ablative recurrent MC HCC have almost the same survival benefit after repeat operations as patients who undergo initial curative resection of HCC. Most hepatocellular carcinomas (HCC) occur in chronic liver disease. Under such conditions, an impaired cellular immune response is often observed, but the mechanisms of this deficiency are unclear. The down-modulation of CD3 z (a key molecule in signal-transducing factor of T cell receptor) leads to a reduction in the function of T cells. Flowcytometrical analysis of CD3 z on peripheral T lymphocytes from 12 HCV infected hosts and 36 HCC bearing patients showed a significantly lower CD3 z expression than normal controls. Compared with tumor infiltrating T lymphocytes (TIL), intrahepatic T lymphocytes (IHL) and peripheral T lymphocytes (PBL) from 11 HCC bearing patients, the expression of CD3 z on TIL was significantly lower than PBL, and the expression level of CD3 z on IHL was almost equal to that on TIL. These results suggest that the down-modulation of CD3 z of T lymphocytes in HCV infected hosts may be one of the reasons why multicentric occurrence and intrahepatic metastasis occur more frequently in HCC patients than another malignancies.