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.
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.
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.
The most commonly used preclinical models of hepatocellular carcinoma (HCC) are limited for use in testing of intra-arterial therapies such as transarterial chemoembolization and radioembolization. Issues encountered with the more commonly used animal models include dissimilarity in their disease development compared with humans and the size of the vasculature which can make intra-arterial therapy testing difficult or impossible. Here we describe the suitability of the woodchuck HCC model for testing of intra-arterial therapies. We describe the techniques for pre-embolization imaging assessment using CT and MRI, technical tips on performing angiography and embolization, and pathological assessment of treated liver.
K E Y W O R D Sangiography, animal model, hepatocellular carcinoma, woodchuck
We present the cast of a 74-year-old woman with a remote history of recurrent localized breast cancer who presented with nonspecific gastrointestinal symptoms who was subsequently found to have metastatic breast cancer in the transverse colon. Nonspecific gastrointestinal complaints can be the first sign of cancer recurrence in these patients. Providers should maintain a high index of suspicion for disease recurrence when evaluating cancer survivors.
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