Objective: To detect circulating hepatocellular carcinoma by demonstrating hepatocellular carcinoma cells or hepatocyte-associated mRNA in the nuclear cell component of peripheral blood (PBL).
Methods: Peripheral blood (5 ml samples were obtained from 93 patients with hepatocellular carcinoma (HCC) and from 33 control subjects (9 with liver cirrhosis after hepatitis B, 14 with chronic hepatitis B, 10 with normal liver function). To identify HCC cells in peripheral blood, liver-specific human alpha-fetoprotein (AFP) mRNA was amplified from total RNA extracted from whole blood by reverse transcription-polymerase chain reaction.
Results: AFPmRNA was detected in 50 blood samples from the HCC patients (50/93, 53.8%). In contrast, there were no clinical control patients whose samples showed detectable AFPmRNA in PBL. The presence of AFPmRNA in blood seemed to be correlated with the stage (by TNM classification) of HCC, the serum AFP value, and the presence of intrahepatic metastasis, portal vein thrombosis, tumor diameter and/or distant metastasis. In addition, AFPmRNA was detected in the blood of 21 patients with metastasis at extrahepatic organs (100%) in contrast to 29 (40.3%) of 72 patients without metastasis.
Conclusion: The presence of AFPmRNA in peripheral blood may be an indicator of malignant hepatocytes, which might predict hematogenous spreading metastasis of tumor cells in patients with HCC.