Prognostic Implications of Arginase and Cytokeratin 19 Expression in Hepatocellular Carcinoma After Curative Hepatectomy: Correlation With Recurrence-Free Survival.

MedStar author(s):
Citation: Gastroenterology Research. 12(2):78-87, 2019 Apr.PMID: 31019617Institution: MedStar Washington Hospital CenterDepartment: Medicine/Internal Medicine | PathologyForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: IN PROCESS -- NOT YET INDEXEDYear: 2019ISSN:
  • 1918-2805
Name of journal: Gastroenterology researchAbstract: Background: The prognostic value of arginase expression in hepatocellular carcinoma (HCC) has been evaluated previously. However, no clear distinction exists yet on the role of arginase-1 as a predictor of recurrence in HCC. Cytokeratin 19 (CK19), a cholangiocytic marker, is occasionally expressed in HCC, but the combination of arginase-1 and CK19 expression has never been evaluated. The aim of the study was to investigate the usefulness of arginase-1 and CK19 expression alone and in combination for prognosticating HCC tumor recurrence after surgical resection.Conclusion: Arginase-1 and CK19 combination immunoreactivity is a potential biomarker of adverse prognosis in HCC, correlating with the presence of multiple tumors, vascular invasion and advanced stage.Methods: Tissue sections from 112 HCCs were immunostained using an automated method and the mouse monoclonal arginase-1 and mouse monoclonal CK19 antibodies. The clinicopathologic variables, including alpha-fetoprotein levels, viral hepatitis, cirrhosis, tumor size, grade and number, vascular invasion, tumor-node-metastasis (TNM) stage, and tumor recurrence and survival, were obtained from each patient's medical records. The variables were assessed for correlation with the immunochemical results. Comparisons of recurrence-free and overall survival were performed using univariate and multivariate regression analyses. A P-value of <= 0.05 was considered statistically significant.Results: High arginase-1 expression was detected in the HCCs of 93 patients (83%), whereas CK19 was positive in the HCCs of only 19 patients (17%). In the univariate analyses, CK19 positivity in HCC was associated with decreased recurrence-free survival compared with CK19-negative HCC (P = 0.0002). Arginase-1 expression was associated with decreased recurrence-free survival when patients were stratified over advanced TNM stage and presence of vascular invasion. The combination of arginase-1 and CK19 expression was a better predictor of decreased recurrence-free survival (P = 0.00008). Arginase-1/CK19 expressions when combined with multiple tumors, TNM stage and vascular invasion were also associated with decreased recurrence-free survival. In the multivariate analysis, tumor grade, CK19 and arginase-1/CK19 expressions were identified as independent prognostic indicators for decreased recurrence-free survival.All authors: Chahine J, deGuzman J, Kallakury B, Ko K, Obiorah IE, Park BUFiscal year: FY2019Digital Object Identifier: Date added to catalog: 2019-05-21
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Journal Article MedStar Authors Catalog Article 31019617 Available 31019617

Background: The prognostic value of arginase expression in hepatocellular carcinoma (HCC) has been evaluated previously. However, no clear distinction exists yet on the role of arginase-1 as a predictor of recurrence in HCC. Cytokeratin 19 (CK19), a cholangiocytic marker, is occasionally expressed in HCC, but the combination of arginase-1 and CK19 expression has never been evaluated. The aim of the study was to investigate the usefulness of arginase-1 and CK19 expression alone and in combination for prognosticating HCC tumor recurrence after surgical resection.

Conclusion: Arginase-1 and CK19 combination immunoreactivity is a potential biomarker of adverse prognosis in HCC, correlating with the presence of multiple tumors, vascular invasion and advanced stage.

Methods: Tissue sections from 112 HCCs were immunostained using an automated method and the mouse monoclonal arginase-1 and mouse monoclonal CK19 antibodies. The clinicopathologic variables, including alpha-fetoprotein levels, viral hepatitis, cirrhosis, tumor size, grade and number, vascular invasion, tumor-node-metastasis (TNM) stage, and tumor recurrence and survival, were obtained from each patient's medical records. The variables were assessed for correlation with the immunochemical results. Comparisons of recurrence-free and overall survival were performed using univariate and multivariate regression analyses. A P-value of <= 0.05 was considered statistically significant.

Results: High arginase-1 expression was detected in the HCCs of 93 patients (83%), whereas CK19 was positive in the HCCs of only 19 patients (17%). In the univariate analyses, CK19 positivity in HCC was associated with decreased recurrence-free survival compared with CK19-negative HCC (P = 0.0002). Arginase-1 expression was associated with decreased recurrence-free survival when patients were stratified over advanced TNM stage and presence of vascular invasion. The combination of arginase-1 and CK19 expression was a better predictor of decreased recurrence-free survival (P = 0.00008). Arginase-1/CK19 expressions when combined with multiple tumors, TNM stage and vascular invasion were also associated with decreased recurrence-free survival. In the multivariate analysis, tumor grade, CK19 and arginase-1/CK19 expressions were identified as independent prognostic indicators for decreased recurrence-free survival.

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