Quantification of alpha(1)-fetoprotein mRNA in peripheral blood and bone marrow: a tool for perioperative evaluation of patients with hepatocellular carcinoma

Background/aims: Quantification of alpha (1)-fetoprotein (AFP) mRNA in the blood using reverse transcriptase polymerase chain reaction (RT-PCR) could be a useful tool in monitoring the dynamics of minimal residual disease in patients with hepatocellular carcinoma (HCC). Since all available assays do not take into account the efficiency of cell separation, RNA extraction an d reverse transcription, a competitive RT-PCR assay for quantification of A FP mRNA in relation to the housekeeping gene glyceraldehyde phosphate dehyd rogenase (GAPBH) was established. Patients and methods Peripheral blood of 22 patients and bone marrow aspirates of ii patients with hepatocellular ca rcinoma was monitored perioperatively. Eighteen patients with other hepatic rumours or non-malignant hepatic diseases rind 26 healthy blood donors ser ved as controls. Messenger RNA contents were calculated relative to the con tent of GAPBH mRNA as an indicator of total cell count, Results: Among HCC patients, 6 of 22 (26%) were positive for AFP mRNA before operation with va lues ranging fi am 2 ag/100 fg to 36 ag/100 fg GAPDH mRNA (mean 14). Among. bone mal row samples, AFP mRNA was detectable in 5 of 11 (45%) cases, with 1 ag/100 fg to 23 ag/100 fg GAPDH (mean ?). However. AFP mRNA was also det ectable in 3 of 18 (17%) control patients and in 2 of 26 (8%) healthy blood donors. Perioperative findings were highly variable. Conclusion: AFP mRNA is not a specific marker for circulating malignant hepatocytes. Whether def inition of a cut-off level or the use of a multimarker-PCR will provide mor e useful data remains to be established.