[440] Arginase 1 Is a Sensitive and Specific Marker for Distinguishing Hepatocellular Carcinoma from Metastatic Tumor

Dana Timek, Jianhui Shi, Haiyan Liu, Fan Lin. Geisinger Medical Center, Danville, PA

Background: Distinction of liver metastatic tumor from hepatocellular carcinoma (HCC) may present a diagnostic challenge, especially in small tissue biopsy or fine needle aspiration (FNA) biopsy specimens. HepPar1 and glypican 3 are useful diagnostic markers, but the expression of these two markers has also been reported in non-hepatocellular tumors. Arginase 1 (ARG1) is a marker for HCC recently described in limited literature. In this study, we compared the expression of these three markers in HCCs and carcinomas from various organs on both surgical and FNA specimens using a single immunostaining system (Dako).
Design: Immunohistochemical evaluation of the expression of ARG1, HepPar1 and glypican 3 was performed on 1,294 cases of carcinomas from various organs on tissue microarray (TMA) sections and 66 cases of liver FNA specimens on cellblocks (29 HCCs; 31 metastatic tumors; and benign liver 6 cases). The staining intensity and distribution were recorded.
Results: The staining results are summarized in Table 1 and Table 2. For the non-hepatocellular tumors (N=1,276), 34 cases (2.7%) and 35 cases (2.7%) were positive for HepPar1 and glypican 3, respectively; in contrast, none was positive for ARG1. For FNA specimens, 20 HCC cases were positive for all three markers, and 8 HCC cases were positive for two markers. Only 1 case was negative for all three markers.

Table 1. Summary of immunostaining results on 1,294 surgical specimens

Diagnosis	ARG1 (positive cases, %)	HepPar 1 (positive cases, %)	Glypican 3 (positive case, %)
HCC (N=18)	17 (94%)	17 (94%)	14 (78%)
Lung AD (N=110)	0	9 (8%)	4 (3.6%)
Lung SCC (N=49)	0	0	9 (18%)
Breast CA (N=171)	0	0	4 (2.3%)
Esophageal CA (N=30)	0	8 (27%)	2 (7%)
Colon CA (N=71)	0	5 (7%)	0
RCC (N=132)	0	0	3 (2.3%)
Pancreas AD (N=50)	0	1 (2%)	0
Prostate AD (N=133)	0	3 (2.3%)	4 (3%)
Endometrial AD (N=38)	0	0	3 (8%)
Neuroendocrine CA (N=76)	0	0	0
Other organs (N= 416)	0	8 (1.9%)	6 (1.4%)

AD–adenocarcinoma; CA-carcinoma

Table 2. Summary of immunostaining results on 66 FNA specimens

Diagnosis	ARG1 (positive cases, %)	HepPar 1 (positive cases, %)	Glypican 3 (positive cases, %)
HCC (N=29)	23 (79%)	24 (83%)	24 (83%)
Metastasis (N=31)	0	0	3 (9.7%)
Benign liver (N=6)	6 (100%)	6 (100%)	1 (17%)

Conclusions: These data demonstrate that Arginase 1 has a similar sensitivity and higher specificity in differentiating a non-hepatocellular carcinoma from HCC when compared to HepPar1 and glypican 3. It is recommended to use three markers as a panel in distinction of HCC from metastatic carcinoma.
Category: Cytopathology

Monday, March 19, 2012 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 52, Monday Morning