Minimal residual disease in primary malignant liver tumors

The failure to reduce the mortality of patients with malignant liver tumors (hepatocellular carcinoma, cholangiocarcinoma) is probably a result of the early dissemination of cancer cells to secondary sites, which is usually m issed by conventional diagnostic procedures used for tumor staging. Recent developments in the field of molecular biology enable us to detect tumor ce lls at a submicroscopic level. Therefore, over the past 10 years, sensitive assays have been developed to detect individual carcinoma cells disseminat ed to regional lymph nodes or distant organs. In contrast to colorectal and also breast cancer where disseminated tumor cells may be of additional pro gnostic value, few data exist for hepatocellular carcinomas. Until now, no relevant studies have been reported for cholangiocarcinoma. Alpha-fetoprote in and also albumin mRNA have been used for the detection of circulating mi crometastatic tumor foci of hepatocellular carcinoma (HCC); however, the in terpretation of the results has been equivocal. If hepatocyte-specific mRNA s are detected in the circulation, it is possible to infer the presence of- circulating, presumably malignant, liver cells. The literature about the in cidence of "micrometastases" and specificity of different assays for hepato cellular carcinomas varies tremendously. This clearly indicates the need fo r uniformity in protocols. For hepatocellular carcinoma, mRNA for alpha-fet oprotein and albumin is not a specific marker of circulating micrometastase s, but may serve for treatment monitoring. Nevertheless, PCR-based techniqu es are a powerful tool in the therapeutical monitoring of hepatocellular ca rcinoma and will find their way into the daily practice of diagnostic histo pathologists in the near future.