Abstract 573: Glypican-3 is a predictive marker for recurrence of hepatocellular carcinoma after surgical resection, especially in early stage

Background and Objective: Even in early stages, recurrence risk of hepatocellular carcinoma (HCC) is high. Glypican-3 (GPC3) is specifically overexpressed in HCC, and its overexpression is correlated with poor prognosis in patients with HCC. Recent studies have shown the utility of GPC3 as a serum and immunohistochemical marker for the diagnosis of HCC. However, the diagnostic value of GPC3 as a predictive marker for recurrence of early-stage HCC is not well understood. Thus, in the present study, we evaluated the usefulness of GPC3 as a predictive marker for recurrence after surgical resection, especially in early-stage HCC. Methods: Plasma samples were collected from 27 patients with stageI HCC who underwent for surgical resection during May 2008 to October 2010. GPC3-expression of surgical specimens was analyzed by immunohistochemical staining. The novel anti-GPC3 mouse monoclonal antibodies were generated and the sandwich enzyme-linked immunosorbent assay (ELISA) system for detection of plasma GPC3 levels was established. Plasma GPC3 concentrations were measured by the developed novel sandwich ELISA system. Plasma samples of age-matched 39 non-liver disease patients were used as control. Results: During follow-up period (median, 738 days), recurrence was observed in 14 cases after surgical resection (51.8%). GPC3 positive rate by the immunohistochemical staining of resected specimen was 53% (13/23). There was a tendency towards a shorter recurrence-free survival (RFS) in GPC3 positive cases than in GPC3 negative cases (p = 0.233). The mean ± standard deviation (SD) of plasma GPC3 concentrations in control subjects was 110.12 ± 37.70 ng/ml, and cut-off value was determined to be 132 ng/ml (mean + 1.5 SD). In stageI HCC, the sensitivity and specificity were 40.7% and 92%, respectively. In the recurrence group, pre-operation plasma GPC3 levels were significantly higher than in the non-recurrence group(median, 191.7 ng/ml vs 29.7 ng/ml, p = 0.029). There was a tendency of shorter RFS in the pre-operation plasma GPC3 positive patients group compared with the negative group (median RFS, 16 months vs not reached), although this difference was not significant (p = 0.127). Among 11 cases remained recurrence-free for over 4 years of follow-up, pre-operation plasma GPC3 positive was only one case. The recurrence rate of patients with post-operation plasma GPC3 positive was significantly higher than GPC3 negative patients (p = 0.033). Conclusions: We have develope