Sensitive detection of circulating hepatocellular carcinoma cells in peripheral venous blood.
BACKGROUND: This study was performed to develop a sensitive method for the detection of circulating hepatocellular carcinoma (HCC) cells in peripheral blood, in advance of the diagnosis of distant metastasis of HCC by conventional means. METHODS: Peripheral blood (5 ml) samples were obtained from 64 patients with HCC and from 48 control subjects (31 patients with benign liver disease, 8 with metastatic liver cancer, and 9 with normal liver function). To identify HCC cells in peripheral blood, liver-specific human alpha-fetoprotein (hAFP) mRNA was amplified from total RNA extracted from whole blood by reverse transcriptase-polymerase chain reaction. RESULTS: Human alpha-fetoprotein mRNA was detected in 23 blood samples from the HCC patients (23/64, 36%), in 17 patients in whom there was no clinical evidence of distant metastasis. In contrast, there were no control patients whose samples showed detectable hAFP mRNA in the peripheral blood. The presence of hAFP mRNA in blood seemed to be correlated with the stage (by TNM classification) of HCC, the serum hAFP value, and the presence of intrahepatic metastasis, portal vein thrombosis, and/or distant metastasis. CONCLUSIONS: Reverse-transcriptase polymerase chain reaction is a very sensitive method for detecting circulating HCC cells. With this technique, important information for the management of HCC can be acquired, such as the indications for orthotopic liver transplantation in HCC patients. Moreover, use of this detection method may encourage investigation of the mechanism of metastasis in HCC.