DETECTION OF ALPHA-FETOPROTEIN MESSENGER-RNA, AN INDICATOR OF HEMATOGENOUS SPREADING HEPATOCELLULAR-CARCINOMA, IN THE CIRCULATION - A POSSIBLE PREDICTOR OF METASTATIC HEPATOCELLULAR-CARCINOMA

We attempted to detect circulating hepatocellular carcinoma by demonst rating hepatocyte-associated mRNA in the nuclear cell component of per ipheral blood using nested reverse transcription-polymerase chain reac tion because of the extremely small number of tumor cells in the circu lation. Albumin mRNA was demonstrated not only in the liver tissue (he patocytes) and HepG2 cells but also in nuclear cells of the blood from normal healthy volunteers (neutrophils and lymphocytes) by reverse tr anscription-polymerase chain reaction. In contrast, alpha-fetoprotein mRNA was demonstrated in the liver tissue, as well as in HepG2 cells, but not in peripheral blood of normal healthy volunteers, indicating t he possibility of using alpha-fetoprotein mRNA for detection of benign and malignant hepatocytes among the population of neutrophils and lym phocytes. alpha-Fetoprotein mRNA in peripheral blood was detected in 1 7 of 33 cases of hepatocellular carcinoma (52%), 2 of 13 cases of cirr hosis (15%) and 2 of 17 cases of chronic hepatitis (12%). alpha-Fetopr otein mRNA was not demonstrated in 26 cases of normal healthy voluntee rs (0%). Among the patients with hepatocellular carcinoma, total volum e of tumor tissue, maximum size of tumor and serum alpha-fetoprotein l evel were markedly increased in the patients with alpha-fetoprotein mR NA in blood. In addition, alpha-fetoprotein mRNA was detected in the b lood of all 6 patients showing metastasis at extrahepatic organs (100% ), in contrast to 11 of 27 cases without metastasis (41%). From these results, we conclude that the presence of alpha-fetoprotein mRNA in pe ripheral blood may be an indicator of circulating malignant or benign hepatocytes, which might predict hematogenous spreading metastasis of tumor cells in patients with hepatocellular carcinoma.