Conclusion: Cdk2 is fully dispensable for advanced HCC progression. However, interventional inactivation of Cyclin E1 in an early stage of HCC development has beneficial effects and attenuates the progres- sion of HCC. Thus, Cyclin E1 could be a promising therapeutic target for treatment of HCC patients. SAT-142 Quantitative comparison of PD-L1 immuno-histochemical assays in hepatocellular carcinoma: The Blueprint-HCC study D.J. Pinato 1 , F. Mauri 1 , P. Spina 1 , O. Cain 2 , A. Siddique 1 , R.D. Goldin 1 , S. Victor 1 , C. Pizio 3 , A. Akarca 4 , R. Boldorini 3 , L. Mazzucchelli 1 , J.R.M. Black 1 , S. Shetty 2 , T. Marafioti 4 , R. Sharma 1 . 1 Imperial College London, Surgery & Cancer, London, United Kingdom; 2 University of Birmingham, Institute of Immunology and Immunotherapy, Birmingham, United Kingdom; 3 Universita’ del Piemonte Orientale “A. Avogadro”, Department of Translational Medicine, Novara, Italy; 4 University College London, Histopathology, London, United Kingdom Email: david.pinato09@imperial.ac.uk Background and Aims: Programmed cell death ligand 1 (PD-L1) expression by immunohistochemistry (IHC) enriches for responses to PD-1/PD-L1 inhibitors across malignancies, however its role as a predictive biomarker in hepatocellular carcinoma (HCC) is elusive and no gold standard assay exists. We evaluated the performance of 4 different PD-L1 detection assays used in landmark clinical studies. Method: PD-L1 IHC was performed on 4 serial sections from tissue microarray (TMA) blocks containing 100 archival cases of HCC that included tumour and surrounding non-tumorous tissue. Antibody clones E1LN3, 28-8, 22c3, SP263 were compared on the basis of percentage and intensity of staining in malignant cells (M) to generate an H-score (range 0–300). Immune cells infiltrating (ICI) and at the periphery, in non-tumoroustissue (ICP) were scored on a 4-tier system (0–3). Results: Patients were 76% males, 20% HCV-positive, 64% cirrhotic with a median age of 67 years. Median tumour size was 4 cm, 70% of patients had T1-T2 tumours and 48% were of grade 2. The proportion of PD-L1 positive cases according to M-ICI-ICP pattern was 2-6-2% for E1LN3, 10-18-19% for 28-8, 9-22-18% for 22c3 and 5-14-13% for SP263. Pairwise comparison of M H-scores revealed heterogeneity across antibodies, with highest concordance between E1L3N/SP263 (R2 = 0.95), E1L3N/22c3 (R2 = 0.65), 22c3/SP263 (R2 = 0.66) and increasing discordance for 28-8/22c3 (R2 = 0.44), E1L3N/28-8 (R2 = 0.29), and 28-8/SP263 (R2 = 0.26). Detection of PD-L1-positive immune infiltrates using a semi-quantitative scoring system revealed significantly different scores in pairwise non-parametric compar- isons of ICI (p < 0.05) but not ICP (p > 0.05 for chi-square test). Conclusion: In Blueprint-HCC we demonstrated that quantification of PD-L1 protein levels in HCC in tumour cells, intra-tumoural and peri-tumoural infiltrate is characterised by significant inter-assay discordance. This has profound implications in the clinical develop- ment of predictive correlates of efficacy to immunotherapy in HCC and sources of such discordance should be explored. SAT-143 Mixed HCC-ICC liver cancer derives from hepatic progenitor cells- A lineage tracing investigation in mouse liver inflammation models N. Rosenberg 1 , N. Barashi 1 , H. Giladi 1 , D. Goldenberg 1 , M. Shoshkes-Carmel 2 , K. Kaestner 3 , M. Van Haele 4 , T. Roskams 4 , E. Galun 1 . 1 Gene Therapy Institute, Hadassah University Hospital, Jerusalem, Israel; 2 Department of Genetics and Center for Molecular Studies in Digestive and Liver Diseases, University of Pennsylvania, Philadelphia, United States; 3 Department of Genetics and Center for Molecular Studies in Digestive and Liver Diseases, Philadelphia, United States; 4 Department of Translational Cell and Tissue Research, University of Leuven, Leuven, Belgium Email: nofar.ros@gmail.com Background and Aims: Primary liver cancer is the second leading cause of cancer-related death worldwide. Primary liver cancer includes: Hepatocellular carcinoma (HCC), intrahepatic cholangio- carcinoma (ICC) and a mixed HCC-ICC tumor. Preceding the development of primary liver cancer, there is usually a prolonged period of chronic inflammation that leads to cirrhosis. It has been proposed that hepatic progenitor cells (HPCs) could contribute to hepatocarcinogenesis. However, this was not proven. These cells proliferate in response to injury and chronic inflammation in the liver. Although stem cells residing in highly proliferative tissues, such as skin, are essential for sustaining normal tissue homeostasis, their contribution in quiescent tissues, such as liver, is still a matter of debate. In this study, we aimed to determine whether HPCs contribute to liver cancer development in the MDR2 KO mouse model of inflammation-induced HCC. Method: In order to enable tracing of progenitor cells, we generated a transgenic mouse based on the MDR2 KO that harbors a YFP reporter gene driven by the Foxl1 promoter, the promoter of a liver progenitor specific marker. These mice (MDR2 KO Foxl1CRE; RosaYFP ) develop chronic inflammation by the age of 1 months and HCC by the age of 16 months and mixed HCC-ICC by the age of 18 months. Results: Using immunofluorescence we show that HPCs are present in the chronically inflamed livers and within dysplastic nodules at the age of a year and later. At the age of 3 months, upon severe inflammation, YFP positive progenitor cells proliferate and also differentiate, giving rise to both cholangiocytes and hepatocytes. Analysis of livers of 16-month MDR2 KO Foxl1CRE;RosaYFP revealed that only a minority of dysplastic nodules were positive for YFP expression. Furthermore, HCC tumors were YFP negative, containing only scattered YFP-positive HPCs, which did not exhibit hepatocyte- like morphology that expressed cancer stem-like cells (CSCs) markers. At late stages of the MDR2 KO model (18-month) these mice developed ICC and HCC-ICC mixed tumors. Surprisingly, the cholangiocytes in tumour cells were YFP positive, implying that they were derived from HPCs. The HCC-ICC YFP positive tumors accounted for 30% of the total tumors observed. Additionally, the YFP cells in the tumors expressed stem cell-like markers including: Epcam, Cd24a and Krt19. These findings recapitulate the characteristics of human ICC-HCC tumors which also have stem cell like features. Conclusion: Taken together, our results suggest that HPCs may not be the origin for HCC but may be the origin for the mixed type HCC-ICC tumors in a chronic inflamed liver model. SAT-144 Circulating exosomal non-coding RNAs as prognostic biomarkers in human hepatocellular carcinoma Y.R. Lee 1 , S.Y. Park 1 , K. Hur 2 , G. Kim 2 , S.Y. Jang 3 , W.Y. Tak 1 , Y.O. Kweon 1 , B. Jeong 1 , G.-E. Kang 1 , S. Seo 1 , J.G. Park 4 , H.W. Lee 5 . 1 Kyungpook National University Hospital, Department of Internal Medicine, Daegu, Korea, Rep. of South; 2 School of Medicine, Kyungpook National University, Department of Biochemistry and Cell Biology, Daegu, Korea, Rep. of South; 3 Kyungpook National University School of Medicine, Internal Medicine, Daegu, Korea, Rep. of South; 4 Yeungnam University Medical Center, Department of Internal Medicine; 5 Dongsan Medical Center, School of Medicine, Keimyung University, Department of Pathology Email: deblue00@naver.com Background and Aims: Exosomal non-coding RNAs (ncRNAs) have unique expression profiles reflecting the characteristics of a tumor, and their role in tumor progression and metastasis is emerging. However, the significance of circulating exosomal ncRNAs in the prognosis of hepatocellularcarcinoma (HCC) remainsto be elucidated. We therefore determined the prognostic significance of circulating exosomal ncRNAs (miRNA-21 and lncRNA-ATB) for human HCC. Method: This prospective study enrolled 79 HCC patients who attended Kyungpook National University Hospital, Republic of Korea between October 2014 and September 2015. Exosomes were extracted from serum samples using the ExoQuick Exosome POSTER PRESENTATIONS S669 Journal of Hepatology 2018 vol. 68 | S605–S842