Abstract 573: Glypican-3 is a predictive marker for recurrence of hepatocellular carcinoma after surgical resection, especially in early stage
Authors: Ofuji Kazuya , Saito Keigo , Nakamoto Yasunari , Nakatsura Tetsuya 
Published: August 2015

Abstract
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 developed a novel ELISA system for detecting plasma GPC3 levels and determined utility of GPC3 as diagnostic marker of HCC. This study suggests GPC3 expression and plasma GPC3 levels might help in identification of patients at high risk of recurrence of HCC after surgical resection, especially in early stage.
Citation Format: Kazuya Ofuji, Keigo Saito, Yasunari Nakamoto, Tetsuya Nakatsura. Glypican-3 is a predictive marker for recurrence of hepatocellular carcinoma after surgical resection, especially in early stage. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 573. doi:10.1158/1538-7445.AM2015-573