Quantitative comparison of alpha-fetoprotein and albumin mRNA levels in hepatocellular carcinoma/adenoma, non-tumor liver and blood: implications in cancer detection and monitoring.

Early detection of recurrence is valuable for monitoring hepatocellular carcinoma (HCC) progression. By quantitative reverse transcriptase polymerase chain reaction (RT-PCR), we derived calibration curves for alpha-fetoprotein (afp) and albumin (alb) mRNAs using 40 matched tumors and non-tumor liver tissues from HCC/adenoma patients. We prospectively quantified tumor cells and non-tumor liver cells in 62 patients' blood samples before, during and after surgery. Expression of both mRNAs was heterogeneous (1-10(5)-fold) between tumors and HepG2 cell line. The alb-mRNA levels in non-tumor liver cells were 2-10-fold higher than in tumor cells. The afp-mRNA levels in HCC cells were 30-1000-fold higher than in non-tumor cells. The alb-mRNA level in blood may reflect the number of liver cells, whereas the afp-mRNA level may represent mostly the number of HCC cells. We found different ratios of circulating HCC cells to non-tumor liver cells during the clinical course of patients, in association with the subsequent development of recurrence/metastasis. This approach may prove useful for detecting and monitoring HCC progression.