OBJECTIVETo assess the level of alpha-fetoprotein (AFP) messenger RNA (mRNA) in peripheral blood of nude mice, and to study its relationship with tumor recurrence and metastasis after curative resection of hepatocellular carcinoma (HCC).

METHODSThe metastatic model of human HCC in nude mice LCI-D20 was used in this study. Curative resection was performed at 10th day after tumor implantation in 28 nude mice. Interferon alpha-1b (IFN alpha-1b) was administered subcutaneously from the next day after resection, at doses of 3 10(7)U/kg/d (8 nude mice), 1.5 10(7) U/kg/d (8 nude mice) respectively in the treatment groups, and normal saline alone in the controlled group (12 nude mice). Thirty-five days after treatment, one milliliter of peripheral blood was taken and AFP mRNA was quantitatively analyzed using TaqMan real-time quantitative RT-PCR. The mice were sacrificed. The size of recurrent tumor was measured and the presence of lung metastases was observed.

RESULTSThe liver recurrent rate, lung metastatic rate and positivity of AFP mRNA in the controlled group were all 100% (12/12), whereas it was 62.5% (5/8), 0% (0/8), 87.5% (7/8) respectively in the IFN alpha-1b 1.5 10(7)U/kg/d treated group. The recurrent tumor in liver of the IFN alpha-1b 1.5 10(7)U/kg/d treated group was much smaller than that of the controlled group (25 mm(3) 2 mm(3) vs 1143 mm(3) 3 mm(3), t =9.27, P<0.01), and the level of AFP mRNA was also lower than that of the controlled group [(85 6)copies/mug vs (955 2) copies/mug, t =4.33, P<0.01]. In the IFN alpha-1b 3 10(7)U/kg/d treated group, there was only one recurrent tumor (0.5 mm(3)), no lung metastasis, and the positivity of AFP mRNA was 0% (?(2)=11.67, P<0.01).

CONCLUSIONSThese results suggest that the level of AFP mRNA in peripheral blood may indicate recurrence and/or metastasis after curative resection of HCC. TaqMan real time quantitative RT-PCR is a very sensitive and convenient method for detecting circulating cancer cells.