Does the presence of circulating hepatocellular carcinoma cells indicate a risk of recurrence after resection?

OBJECTIVES: Alpha-fetoprotein messenger RNA (AFP mRNA) in the peripheral blood (PB) of patients with hepatocellular carcinoma (HCC) has been considered to represent isolated tumor cells. We investigated its association with the prognosis after curative resection. METHODS: Using a reverse-transcription polymerase chain reaction (RT-PCR)-based assay, AFP mRNA in the PB was determined prospectively in control and in 81 patients with curative resection for HCC. RESULTS: Twenty-two (27.2%) and 19 (23.4%) of 81 HCC patients had AFP mRNA in their pre- and postoperative PB. Its presence preoperatively was not associated with an increased risk of HCC recurrence (54.5% vs 40.7%, p = 0.264). In contrast, the postoperative presence associated significantly with a higher incidence of recurrence (89.5% vs 30.6%, p < 0.001), irrespective of preoperative status. The odds ratio for HCC recurrence was 19.2 (95% confidence interval [CI]: 4.0-91.7). The cumulative probability of recurrence-free survival was also much lower in patients with postoperatively positive AFP mRNA (p < 0.001). The Cox proportional hazards model also demonstrated a significant association with recurrence (p = 0.002). Preoperative serum AFP is also a significant factor and combination with postoperative AFP mRNA enhances the predictability, sensitivity (75.0%), specificity (93.3%), positive prediction (90.0%), and negative prediction (82.4%). CONCLUSIONS: The postoperative detection of AFP mRNA in PB is associated with an increased risk of earlier HCC recurrence. Combination with preoperative serum AFP is useful in predictability.