Abstract 4688: Novel prognostic subtype of hepatocellular carcinoma reflecting stem/maturational status of the tumor defined by Gd-EOB-DTPA-enhanced MRI and serum AFP

Abstract

Abstract Survival of patients with hepatocellular carcinoma (HCC) varies on an individually basis, even after surgery for early-stage tumors. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (EOB-MRI) has recently been introduced to evaluate hepatic lesions with regard to the activity of the organic anion transporter OATP1B3 as well as vascularity. Here we report that Gd-EOB-DTPA-Enhanced MRI and serum alpha-fetoprotein (AFP) status reflects the stem/maturation status of HCC with distinct biology and prognostic information. Atypical uptake of Gd-EOB-DTPA in the hepatobiliary phase was observed in ∼ 15% of HCCs. This uptake correlated with the low serum alpha-fetoprotein (AFP) levels, maintenance of hepatocyte function with the up-regulation of OATP1B3 and HNF4A, and good prognosis. In contrast, HCC showing reduced Gd-EOB-DTPA uptake with high serum AFP presented poor prognosis with the activation of an oncogene FOXM1. Knockdown of HNF4A in cancer cells, obtained from a surgically resected HCC showing atypical uptake of Gd-EOB-DTPA, resulted in the increase of AFP and FOXM1 and the loss of OATP1B3 expression accompanied with the mesenchymal morphological changes, enhanced cell proliferation and tumorigenesis in vivo. HCC classification based on EOB-MRI and serum AFP level (EOB-AFP classification) predicted overall survival in a retrospective cohort (n = 70), and its prognostic utility was validated in a multi-institution cohort of early-stage HCCs (n = 109). This non-invasive classification system is molecularly based on the stem/maturation status of HCCs and can be incorporated into current staging to improve management algorithms, especially in early stage. Citation Format: Taro Yamashita, Masao Honda, Shuichi Kaneko. Novel prognostic subtype of hepatocellular carcinoma reflecting stem/maturational status of the tumor defined by Gd-EOB-DTPA-enhanced MRI and serum AFP. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4688. doi:10.1158/1538-7445.AM2014-4688