The diagnostic value of arginase-1 immunostaining in differentiating hepatocellular carcinoma from metastatic carcinoma and cholangiocarcinoma as compared to HepPar-1
The ability to distinguish hepatocellular carcinoma (HCC) from metastatic carcinoma (MC) involving the liver and cholangiocarcinoma (CC) by immunohistochemistry has been limited by the lack of a reliable positive marker for hepatocellular differentiation. Arginase-1 is a marker for HCC recently described in some literature.
To examine the immunohistochemical staining of arginase-1 in cases of HCC, MC involving the liver and CC as compared to hepatocyte paraffin antigen -1 (HepPar-1) in an attempt to further define the diagnostic utility of arginase-1 in differentiating these tumors.
Materials and methods
A comparative immunohistochemical study of arginase-1 and HepPar-1expression was performed in 50 HCC cases, 38 cases of MC to the liver from varying sites, 12 cases of CC and 10 specimens of normal liver tissues. The predictive capacity of arginase-1 and HepPar-1 staining was determined using sensitivity, specificity, positive predictive value, and negative predictive value calculations.
All normal liver tissues (no=10), non- neoplastic cirrhotic liver tissues adjacent to HCC (no=42) as well as those adjacent to MC (no= 9) showed diffuse and strong immunostaining for both arginase-1 and HepPar-1. Arginase-1 demonstrated positive immunoreactivity in 42 of 50 (84%) cases of HCC compared with 35 of 50 (70%) for HepPar-1. Only one of 38 (2.6%) cases of MC and one of 12 (8.3%) cases of CC showed positive immunoreactivity for arginase-1. In contrast, HepPar-1 immunoreactivity was detected in 6 of 38 (15.8%) cases of MC and in 2 of 12 (16.7%) cases of CC. Arginase -1 showed a significantly higher sensitivity for HCC diagnosis (84%) compared to HepPar -1(70%) (p=0.016). The specificity of arginase-1 for HCC diagnosis was higher (96%) than that of HepPar -1 (84%); nevertheless, this was not statistically significant (p=0.109). Howerver, the combination of both immunomarkers for the diagnosis of HCC, raised the specificity to 100%.
Arginase-1 immunostaining has a higher sensitivity and specificity than HepPar-1 for HCC diagnosis. Furthermore, the combined use of arginase-1 and HepPar-1 can provide a potentially promising tool to improve the accuracy in distinguishing HCC from metastatic carcinoma and cholangiocarcinoma.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9991436558072434.
- Waly Raphael, S, Yangde, Z, Yuxiang, C (2012) Hepatocellular carcinoma: focus on different aspects of management. ISRN Oncol 2012: pp. 421673
- Anwar, WA, Khaled, HM, Amra, HA, El-Nezami, H, Loffredo, CA (2008) Changing pattern of hepatocellular carcinoma (HCC) and its risk factors in Egypt: possibilities for prevention. Mutat Res 659: pp. 176-184
- Aleem, E, Elshayeb, A, Elhabachi, N, Mansour, AR, Gowily, A, Hela, A (2012) Serum IGFBP-3 is a more effective predictor than IGF-1 and IGF-2 for the development of hepatocellular carcinoma in patients with chronic HCV infection. Oncol Lett 3: pp. 704-712
- Lamps, LW, Folpe, AL (2003) The diagnostic value of hepatocyte paraffin antibody 1 in differentiating hepatocellular neoplasms from nonhepatic tumors: a review. Adv Anat Pathol 10: pp. 39-43 CrossRef
- Fujiwara, M, Kwok, S, Yano, H, Pai, RK (2012) Arginase-1 is a more sensitive marker of hepatic differentiation than HepPar-1 and glypican-3 in fine-needle aspiration biopsies. Cancer Cytopathol 120: pp. 230-237 CrossRef
- Yan, BC, Gong, C, Song, J, Krausz, T, Tretiakova, M, Hyjek, E, Al-Ahmadie, H, Alves, V, Xiao, SY, Anders, RA, Hart, JA (2010) Arginase-1: a new immunohistochemical marker of hepatocytes and hepatocellular neoplasms. Am J Surg Pathol 34: pp. 1147-1154 CrossRef
- Kakar, S, Gown, AM, Goodman, ZD, Ferrell, LD (2007) Best practices in diagnostic immunohistochemistry: hepatocellular carcinoma versus metastatic neoplasms. Arch Pathol Lab Med 131: pp. 1648-1654
- Lau, SK, Prakash, S, Geller, SA, Alsabeh, R (2002) Comparative immunohistochemical profile of hepatocellular carcinoma, cholangiocarcinoma,and metastatic adenocarcinoma. Hum Patho 33: pp. 1175-1181 CrossRef
- Chu, PG, Ishizawa, S, Wu, E, Weiss, LM (2002) Hepatocyte antigen as a marker of hepatocellular carcinoma: an immunohistochemical comparison to carcinoembryonic antigen, CD10, and alpha-fetoprotein. Am J Surg Pathol 26: pp. 978-988 CrossRef
- Kakar, S, Muir, T, Murphy, LM, Lloyd, RV, Burgart, LJ (2003) Immunoreactivity of Hep Par 1 in hepatic and extrahepatic tumors and its correlation with albumin in situ hybridization in hepatocellular carcinoma. Am J Clin Pathol 119: pp. 361-366 CrossRef
- Minervini, MI, Demetris, AJ, Lee, RG, Carr, BI, Madariaga, J, Nalesnik, MA (1997) Utilization of hepatocyte-specific antibody in the immunocytochemical evaluation of liver tumors. Mod Pathol 10: pp. 686-692
- Wang, L, Vuolo, M, Suhrland, MJ, Schlesinger, K (2006) HepPar1, MOC-, pCEA, mCEA and CD10 for distinguishing hepatocellular carcinoma vs. metastatic adenocarcinoma in liver fine needle aspirates. Acta Cytol 50: pp. 257-262 CrossRef
- Fan, Z, van de Rijn, M, Montgomery, K, Rouse, RV (2003) Hep par 1 antibody stain for the differential diagnosis of hepatocellular carcinoma: 676 tumors tested using tissue microarrays and conventional tissue sections. Mod Pathol 16: pp. 137-144 CrossRef
- Leong, AS, Sormunen, RT, Tsui, WM, Liew, CT (1998) Hep Par 1 and selected antibodies in the immunohistological distinction of hepatocellular carcinoma from cholangiocarcinoma, combined tumours and metastatic carcinoma. Histopathology 33: pp. 318-324 CrossRef
- Aviel-Ronen, S, Lau, SK, Pintilie, M, Lau, D, Liu, N, Tsao, MS, Jothy, S (2008) Glypican-3 is overexpressed in lung squamous cell carcinoma, but not in adenocarcinoma. Mod Pathol 21: pp. 817-825 CrossRef
- Zynger, DL, Everton, MJ, Dimov, ND, Chou, PM, Yang, XJ (2008) Expression of glypican 3 in ovarian and extragonadal germ cell tumors. Am J Clin Pathol 130: pp. 224-230 CrossRef
- Hishinuma, M, Ohashi, KI, Yamauchi, N, Kashima, T, Uozaki, H, Ota, S, Kodama, T, Aburatani, H, Fukayama, M (2006) Hepatocellular oncofetal protein, glypican 3 is a sensitive marker for alpha-fetoprotein- producing gastric carcinoma. Histopathology 49: pp. 479-486 CrossRef
- Choi, S, Park, C, Ahn, M, Lee, JH, Shin, T (2012) Immunohistochemical study of arginase 1 and 2 in various tissues of rats. Acta Histochem 114: pp. 487-494 CrossRef
- Multhaupt, H, Fritz, P, Schumacher, K (1987) Immunohistochemical localisation of arginase in human liver using monoclonal antibodies against human liver arginase. Histochemistry 87: pp. 465-470 CrossRef
- Sekine, S, Ogawa, R, Mcmanus, MT, Kanai, Y, Hebrok, M (2009) Dicer is required for proper liver zonation. J Pathol 219: pp. 365-372 CrossRef
- Theise, ND, Curado, MP, Franceschi, S Hepatocellular carcinoma. In: Bosman, FT, Carneiro, F, Hruban, RH, Theise, ND eds. (2010) WHO Classification of Tumors of the Digestive System. IARC Press, Lyon, France, pp. 205-216
- Shiran, MS, Isa, MR, Sherina, MS, Rampal, L, Hairuszah, I, Sabariah, AR (2006) The utility of hepatocyte paraffin 1 antibody in the immunohistological distinction of hepatocellular carcinoma from cholangiocarcinoma and metastatic carcinoma. Malays J Pathol 28: pp. 87-92
- Hajósi-Kalcakosz, S, Dezső, K, Bugyik, E, Bödör, C, Paku, S, Pávai, Z, Halász, J, Schlachter, K, Schaff, Z, Nagy, P (2012) Enhancer of zeste homologue 2 (EZH2) is a reliable immunohistochemical marker to differentiate malignant and benign hepatic tumors. Diagn Pathol 7: pp. 86 CrossRef
- Hong, H, Patonay, B, Finley, J (2011) Unusual reticulin staining pattern in well-differentiated hepatocellular carcinoma. Diagn Pathol 6: pp. 15 CrossRef
- Timek, DT, Shi, J, Liu, H, Lin, F (2012) Arginase-1, HepPar-1, and Glypican-3 Are the Most Effective Panel of Markers in Distinguishing Hepatocellular Carcinoma From Metastatic Tumor on Fine-Needle Aspiration Specimens. Am J Clin Pathol 138: pp. 203-210 CrossRef
- McKnight, R, Nassar, A, Cohen, C, Siddiqui, MT (2012) Arginase-1: a novel immunohistochemical marker of hepatocellular differentiation in fine needle aspiration cytology. Cancer Cytopathol 120: pp. 223-229 CrossRef
- Taylor, SL, Haque, S (2011) Hepatobiliary pathology. Curr Opin Gastroenterol 27: pp. 248-255 CrossRef
- Guo, X, Xiong, L, Zou, L, Sun, T, Zhang, J, Li, H, Peng, R, Zhao, J (2012) L1 cell adhesion molecule overexpression in hepatocellular carcinoma associates with advanced tumor progression and poor patient survival. Diagn Pathol 7: pp. 96 CrossRef
- Guo, X, Xiong, L, Sun, T, Peng, R, Zou, L, Zhu, H, Zhang, J, Li, H, Zhao, J (2012) Expression features of SOX9 associate with tumor progression and poor prognosis of hepatocellular carcinoma. Diagn Pathol 7: pp. 44 CrossRef
- Schmilovitz-Weiss, H, Tobar, A, Halpern, M, Levy, I, Shabtai, E, Ben-Ari, Z (2011) Tissue expression of squamous cellular carcinoma antigen and Ki67 in hepatocellular carcinoma-correlation with prognosis: a historical prospective study. Diagn Pathol 6: pp. 121 CrossRef
- Chu, PG, Weiss, LM (2004) Immunohistochemical characterization of signet-ring cell carcinomas of the stomach, breast, and colon. Am J Clin Pathol 121: pp. 884-892 CrossRef
- Wennerberg, AE, Nalesnik, MA, Coleman, WB (1993) Hepatocyte paraffin 1: a monoclonal antibody that reacts with hepatocytes and can be used for differential diagnosis of hepatic tumors. Am J Pathol 143: pp. 1050-1054
- Iida, H, Hata, M, Kakuno, A, Hirano, H, Yamanegi, K, Yamada, N, Ohyama, H, Terada, N, Yasui, C, Yamanaka, N, Nakasho, K (2011) Expression of hepatocyte markers in mass-forming peripheral and periductal-infiltrating hilar intrahepatic cholangiocarcinomas. Oncol Lett 2: pp. 1041-1046
- Cao, W, Sun, B, Feitelson, MA, Wu, T, Tur-Kaspa, R, Fan, Q (2009) Hepatitis C virus targets over-expression of arginase I in hepatocarcinogenesis. Int J Cancer 124: pp. 2886-2892 CrossRef
- The diagnostic value of arginase-1 immunostaining in differentiating hepatocellular carcinoma from metastatic carcinoma and cholangiocarcinoma as compared to HepPar-1
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
- Online Date
- October 2012
- Online ISSN
- BioMed Central
- Additional Links
- Hepatocellular carcinoma
- Metastatic carcinoma