Arginase-1: A New Rabbit Monoclonal Antibody Is a Superior Marker in Differentiating Primary Hepatocellular Carcinoma vs. Tumors Metastatic to the Liver
Bhuvnesh K Sharma, Ding Zhou, Ryan Bremer, Thomas Haas, David Tacha. Biocare Medical, LLC, Concord, CA; Mercy Hospital, Janesville, WI
Background: Identification of a more sensitive and specific diagnostic marker delineating primary HCC from tumors metastatic to the liver is of immense clinical significance. Arginase-1 (ARG-1), a urea cycle metalloenzyme found in liver, is now a key target for the differential diagnosis of HCC from metastatic tumors to the liver. An ARG-1 rabbit polyclonal antibody (Sigma) is commercially available for immunohistochemistry (IHC); however, only limited studies on liver cancers and cancers metastatic to the liver have been published. In a comparison IHC study, we will evaluate the efficacy of several commercially available ARG-1 antibodies in HCC.
Design: Sensitivity and specificity of 6 monoclonal/polyclonal antibodies to ARG-1 were determined using tissue microarrays (TMAs). A total of 957 neoplastic and normal tissues were examined in order to determine their suitability in differential diagnosis in liver tumors. For a direct IHC comparison, the referenced ARG-1 rabbit polyclonal antibody, Hep Par1, and TTF-1 antibodies were evaluated in 209 cases of HCC.
Results: Only a rabbit monoclonal antibody (RMab) ARG-1 was suitable for comparison to the referenced ARG-1. Staining patterns that consist of both cytoplasmic and nuclear staining were similar with both ARG-1 antibodies; however the ARG-1 RMab staining sensitivity was improved in grades II and III HCC [Table 1]. Staining sensitivity of ARG-1 RMab was also superior to TTF-1 (p<0.0001) and HepPar-1 (p<0.0015) [Table 2]. None of the studied neoplasms commonly metastatic to the liver were found to be immunoreactive to ARG-1 RMab, except in a very low percentage of pancreas and prostate malignancies. ARG-1 RMab stained 7/14 of cholangiocarcinomas; and in some HCC, staining of inflammatory cells was observed.
|ARG-1 antibody||Grade I||Grade II||Grade III|
|RMab||100% (15/15)||96.6% (28/29)||75.0% (9/12)|
|Reference Antibody||100% (15/15)||86.2% (25/ 29)||66.7% (8/12)|
|Tumor Grade||ARG-1||Hep Par-1||TTF-1|