α-fetoprotein,vascular endothelial growth factor receptor-1 and early recurrence of hepatoma

AIM:To investigate whether α-fetoprotein (AFP) and vascular endothelial growth factor receptor (VEGFR)-1 correlate with early recurrence of hepatoma/hepatocel-lular carcinoma (HCC).METHODS:From 2000 to 2005,114 consecutive pa-tients with HCC underwent primary curative hepatecto-my.The mean age was 60.7 (8.7) years and 94 patients were male.The median follow-up period was 71.2 mo (range:43-100 mo).Immediately prior to commencing laparotomy,5 mL bone marrow was aspirated from thesternum and collected in citrate-coated test tubes.The initial 2 mL of bone marrow aspirate was discarded in each case.AFP mRNA and VEGFR-1 mRNA in the bone marrow and peripheral blood (BM-and PH-AFP mRNA and BM-and PH-VEGFR-1 mRNA,respectively) were measured by real-time quantitative reverse transcription polymerase chain reaction.As normal controls,VEGFR-1 mRNA in the bone marrow and peripheral blood was also measured in 11 living liver donors.These data were evaluated for any correlation with early recurrence,comparing clinical and pathological outcomes.RESULTS:The cut-off value of the BM-AFP mRNA and PH-AFP mRNA level in patients with HCC was set at 1.92 × 10-7 and zero,respectively,based on data from the controls.A total of 34 (29.8%) and six (5.4%) patients were positive for BM-AFP mRNA and PH-AFP mRNA,respectively.The BM-VEGFR-1 mRNA levels in all HCC patients were higher than those in the normal con-trols,and this was the case also for PH-VEGFR-1mRNA.The 25-percentile values for the BM-and PH-VEGFR-1 mRNA in HCC patients were used as the cut-off values for assigning the patients into two groups based on these transcript levels.The High group for BM-VEG-FR-1 mRNA contained 81 (71.1%) HCC cases and the Low group was assigned 33 (28.9%) patients.These numbers for PH-VEGFR-1mRNA were 78 (75.0%) and 26 (25.0%),respectively.HCC recurred in 80 patients;in the remnant liver in 48 cases,in the remnant liver and remote tissue in 20,and in the remote tissue alone in 12.BM-AFP mRNA-positive cases showed a signifi-cantly higher rate of early recurrence (within 1 year of surgical treatment) compared with BM-AFP mRNA-negative patients (P=0.0091).Patients were classified into four groups according to the level/status of their BM-VEGFR-1 and BM-AFP mRNA as follows:group A (n=23),BM-VEGFR-1/BM-AFP mRNA=low/negative;group B (n=57) high/negative;group C (n=10) low/positive;group D (n=24),high/positive.This classifi-cation was found to correlate with a recurrence of thisdisease within 1 year (P=0.0228).The disease-free survival curve of group A was significantly better than that of groups B,C or D (P=0.0437,P=0.0325,P=0.0225).No other classification (i.e.,PH-VEGF-R1/BM-AFP,BM-VEGF-R1/PH-AFP,and PH-VEGF-R1/PH-AFP mRNA) showed such a correlation.CONCLUSION:The evaluation of BM-AFP and BM-VEG-FR-1 mRNA in patients with HCC may be a valuable pre-dictor of disease recurrence following curative resection.