α-Fetoprotein (AFP) messenger RNA (mRNA) in the peripheral blood of patients with hepatocellular carcinoma (HCC) may indicate hematogenous spread of HCC. This study examined the presence of AFP mRNA in the blood of 148 patients, in terms of clinical parameters, tumor metastasis and survival rate. For the prospective study, 109 patients with HCC were followed in the period between March 1996 and March 1999. AFP mRNA in the blood was examined by means of nested reverse transcription polymerase chain reaction. AFP mRNA was detected in the blood in 23 (15.5%) of 148 patients with HCC. AFP mRNA in the blood was significantly correlated with protein induced by vitamin K absence or antagonist II level, higher AFP level (200 IU/mL or more) and extrahepatic metastases, but not with tumor size, number of tumor nodules or tumor-nodule-metastasis stage. This prospective study confirmed that intra- and extra-hepatic metastases developed more frequently in the 22 AFP mRNA-positive patients than in the 87 AFP mRNA-negative patients (P < 0.01). The cumulative survival rate was significantly lower in the former than in the latter (P < 0.01). In conclusion, AFP mRNA in the blood is closely related to hematogenous spread and might be a good predictor of metastasis and poorer survival rate in HCC patients
