Circulating messenger RNA of α-fetoprotein: A possible risk factor of recurrence after resection of hepatocellular carcinoma

Hypothesis: Isolated tumor cells may be associated with micrometastasis. Circulating α-fetoprotein messenger RNA (AFP mRNA) in patients with hepatocellular carcinoma (HCC) has been considered to represent isolated tumor cells. We propose that circulating AFP mRNA may have prognostic value after curative resection of HCC. Design: A prospective cohort study. Setting: Referral center. Patients: Eighty-one consecutive patients who underwent curative resection of HCC. Measurements: A nested reverse-transcriptase polymerase chain reaction (RT-PCR) assay for circulating AFP mRNA before and again 12 weeks after surgery in 81 patients and in a control group. Clinicopathological variables and postoperative course (recurrence and recurrence-free survival) were examined for correlation with the levels of circulating AFP mRNA. Results: Of the 81 patients, 22 (27.2%) and 19 (23.4%) had AFP mRNA detected preoperatively and postoperatively, respectively. The recurrence-free survival at 1, 2, and 3 years after resection was significantly shorter in the latter patients (52.6%, 15.6%, and 0%, respectively; P <.001) but not in the former (81.8%, 54.5%, and 29.2%; P = .28). In univariate analysis, a significantly higher recurrence rate was found in patients with liver cirrhosis (P = .03), Edmondson-Steiner differentiation grade III or IV (P <.001), incomplete or absent capsule (P = .001), vascular invasion (P <.001), daughter nodules (P = .003), or a positivity for postoperative circulating AFP mRNA (P <.001). Postoperative positivity for circulating AFP mRNA remained a significant risk factor (P = .002; hazard ratio 3.13; 95% confidence interval, 1.52-6.47) in the multivariate analysis. Conclusion: The detection of circulating AFP mRNA 12 weeks postoperatively is associated with an increased and earlier risk of HCC recurrence.