Abstract 4878: Prognostic significance of Arginase and CK19 expression in human hepatocellular carcinoma after surgical resection: Correlation with recurrence-free survival

Abstract

Abstract Background. Arginase-1 is an enzyme that is responsible for the conversion of arginine to urea in the urea cycle. A previous study has shown prognostic value of arginase expression in HCC following surgical resection. However, clear distinction on the role of arginase-1 as a predictor of recurrence in hepatocellular carcinoma remains unanswered. Occasionally, CK19, a cholangiocytic marker can be expressed in HCC, but the combination of arginase-1 and CK19 expression has never been evaluated. In this study, we investigate the usefulness of arginase-1 and CK19 expression alone and in combination in the determination of tumor recurrence following surgical resection in patients with HCC. Design: Formalin-fixed paraffin embedded tissue sections from 112 HCCs were immunostained by an automated method (DAKO enVision + Dual Link System-HRP) using mouse monoclonal Arginase-1 (clone SL6ARG, Dako) and mouse monoclonal CK19 (clone RCK108, invitrogen). Nuclear and/or cytoplasmic reactivity was scored based on the intensity and percentage of positive cells in the tumor cells. Arginase-1 expression was separated into high (intense diffuse or regional positivity in > 50% of tumor cells) and low (weak or negative expression). The clinicopathologic variables including recurrence and survival were obtained from the patients charts and were correlated with the immunochemical results. Results: High arginase-1 expression was detected in 93 patients (83%), whereas CK19 was positive in 19 patients (17%). In the univariate analyses, CK19 positivity (+) in HCC was associated with decreased recurrence free survival when compared with CK19 negative HCC (P=0.001). Arginase-1 expression was not associated recurrence-free and overall survival. However, the combination of arginase-1 and CK19 is associated with decreased recurrence-free survival (p<0.001). Furthermore, Arginase-1/CK19+ combined with TNM staging (p=0.042), vascular invasion (p<0.001) multiple tumor numbers (p=0.02) may play a role as additional predictors of recurrence-free survival. In the multivariate analysis, TNM stage, vascular invasion and CK19 were identified as independent prognostic indicators for recurrence-free survival. In addition, vascular invasion was an independent prognostic predictor of overall survival. Conclusion: The combination of arginase-1 and CK19 immunoreactivity are potential biomarkers of adverse prognosis in HCC, correlating with presence of multiple tumors, vascular invasion and advanced stage. The results of this study may explain why clear beneficial effects of recombinant human arginase have not been demonstrated in clinical studies. Further study of arginase expression and its potential role as a therapeutic target in HCC appear warranted. Citation Format: Ifeyinwa E. Obiorah, Joeffery Chahine, Kyungmin Ko, ByoungUk Park, Jose deGuzman, Bhaskar Kallakury. Prognostic significance of Arginase and CK19 expression in human hepatocellular carcinoma after surgical resection: Correlation with recurrence-free survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4878.