[400] Arginase-1: A Novel Immunohistochemical (IHC) Marker of Hepatocellular Differentiation in Fine Needle Aspiration (FNA) Cytology

Ryan McKnight, Cynthia Cohen, Aziza Nassar, Momin T Siddiqui. Emory University School of Medicine, Atlanta, GA; Mayo Clinic College of Medicine, Rochester, MN

Background: FNA biopsy under radiologic guidance is a safe and effective method of assessing lesions in the liver. Unfortunately, diagnostic pitfalls exist in the distinction of hepatocellular carcinoma (HCC) from other primary and metastatic mass lesions in liver FNA specimens as a result of limited sample size, the absence of full architectural detail, and the presence of significant cytomorphologic overlap. Arginase-1 (AG-1) is a urea cycle enzyme that has demonstrated usefulness as an IHC marker of hepatocellular differentiation. Previous studies have reported the efficacy of HepPar-1 (HP-1) and glypican-3 (GPC-3) IHC in liver FNA cytology. To our knowledge, no studies using AG-1 IHC have been performed on FNA specimens, and its performance characteristics have not yet been compared with HP-1 and GPC-3 IHC.
Design: IHC for AG-1, HP-1, and GPC-3 were performed on cell block sections from 92 liver FNAs including HCC (n=44), cirrhosis (n=2), focal nodular hyperplasia (FNH) (n=3), hepatic adenoma (HA) (n=2), dysplastic nodule (DN) (n=6) and metastatic carcinoma (MC) to the liver (n=35). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the cytology results were calculated for all immunomarkers in detecting HCC from non-HCC lesions.
Results: AG-1 IHC staining was generally intense and expressed more frequently in HCC (84.1%) compared with HP-1 (72.7%) and GPC-3 (56.8%). AG-1 and HP-1 expression was also observed in all cases (100%) of cirrhosis, FNH, HA, and DN, while GPC-3 expression was absent. All three immunomarkers were negative in MC.

AG-1, HP-1, and GPC-3 expression in HCC and non-HCC lesions

	HCC (n=44)	Other (n=48)
AG-1	37 (84.1%)	14 (29.2%)
HP-1	32 (72.7%)	14 (29.2%)
GPC-3	25 (56.8%)	0 (0%)

Sensitivity, Specificity, PPV, and NPV of AG-1, HP-1, and GPC-3 in distinguishing HCC from non-HCC lesions

	AG-1 (%)	HP-1 (%)	GPC-3 (%)
Sensitivity	84.1	72.7	56.8
Specificity	70.8	70.8	100
PPV	72.5	69.6	100
NPV	82.9	73.9	71.6

Conclusions: The results of the study demonstrate that both AG-1 and HP-1 are effective IHC markers of hepatocellular differentiation. AG-1 demonstrates superior sensitivity compared with HP-1 and GPC-3 in the diagnosis of HCC. GPC-3 demonstrates superior specificity. These results suggest that the utilization of AG-1 and HP-1, in combination with GPC-3, can aid in the diagnosis of HCC and be used to distinguish HCC from MC.
Category: Cytopathology

Monday, March 19, 2012 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 55, Monday Morning