Diagnostic role of glypican 3 and CD34 for differentiating hepatocellular carcinoma from nonmalignant hepatocellular lesions Eman Tawfik Enan, MD, Amira Kamal El-Hawary, PhD ⁎, Dina Abd El-Aziz El-Tantawy, PhD, Maha Mohamed Abu-Hashim, PhD, Nagwa Mokhtar Helal, PhD Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt abstract article info Keywords: Combined Glypican 3 CD34 Hepatocellular carcinoma Well-differentiated hepatocellular carcinoma (HCC) may be difficult to distinguish from a benign lesion. Glypican 3 (GPC-3) is an oncofetal protein, which has been demonstrated to be up-regulated in HCC. The aim of this study is to evaluate the diagnostic role of combined GPC-3 and CD34 immunoassaying in the distinction between HCC and benign hepatic mimickers. This study was performed on 100 cases of formalin-fixed, paraffin-embedded cases of hepatic focal lesions obtained from the files of pathology laboratory of our university from 2009 to 2012. The following groups were studied: group A (n = 60) (hepatocellular malignant lesions) and group B (n = 40) (Hepatocellular nonmalignant lesions). All cases were stained with GPC-3 and CD34. Sensitivity, specificity, and positive and negative predictive values were calculated for both antibodies. Glypican 3 and complete CD34 staining pattern expression in group A was significantly higher than in group B. The results of costaining showed that, in HCCs, almost all the GPC-3–positive cases had a complete CD34 staining pattern, whereas in the 40 hepatocellular nonmalignant lesions, none stained up with the 2 markers. Therefore, although the sensitivity declined (82%), the specificity and positive predictive value (PPV) of costaining reached 100% and were greater than that observed for single staining with GPC-3 (specificity, 92.5%; PPV, 94.3%) or CD34 (specificity, 97.5%; PPV, 98.3%). Our data demonstrate that GPC-3 and CD34 costaining has better diagnostic value for differentiating HCC from nonmalignant hepatocellular lesions than does single staining. © 2013 Elsevier Inc. All rights reserved. 1. Introduction Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and its prognosis depends largely on early detection and management [1]. In Egypt, the incidence of HCC has doubled in the past 10 years, thus becoming the second most incident and lethal cancer in men [2]. With the advancement of imaging analysis techniques, more and more oncologists are detecting hepatic nodular lesions and having them biopsied for the pathologic diagnosis of HCC [3]. The differential diagnosis of HCC varies, depending on the degree of tumor differentiation. For example, well-differentiated HCC may be difficult to distinguish from a benign lesion such as hepatic adenoma in a noncirrhotic liver or dysplastic nodule in the setting of cirrhosis [4]. Most markers of hepatocellular differentiation such as Hep Par 1 and polyclonal carcinoembryonic antigen do not distinguish between benign and malignant hepatocellular lesions. Alpha fetoprotein is expressed in HCC, but its sensitivity is low (20%-30%), limiting its diagnostic potential [5]. Glypican 3 (GPC-3) is an oncofetal protein and is a member of the membrane-bound heparin sulfate proteoglycans. Glypican 3 is expressed in fetal tissues and trophoblastic cells and has little or no expression in liver adult tissues [4]. It is expressed in 64% to 90% of HCC [3]. Expression of GPC-3 has not been observed in benign hepatocellular lesions by in situ hybridization or immunohistochem- istry [6,7]. CD34 is one of the most useful immunohistochemical markers in the distinction between benign and malignant hepatocellular lesions. Normal sinusoidal lining cells do not stain for CD34, whereas the abnormal capillaries of HCCs are diffusely CD34 positive. Low-grade dysplastic nodules and regenerative cirrhotic nodules can show some CD34 staining at the periphery and periportal areas [8]. The aim of this study is to evaluate the diagnostic role of combined GPC-3 and CD34 immunoassaying in the distinction between HCC and benign hepatic mimickers. 2. Materials and methods This study was performed on 100 cases of formalin-fixed, paraffin- embedded cases of hepatic focal lesions obtained from the files of pathology laboratory of our university from 2009 to 2012. Twenty specimens were trucut needle biopsy, 40 were from partial Annals of Diagnostic Pathology 17 (2013) 490–493 ⁎ Corresponding author. Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt. Tel.: +20123764602. E-mail address: amira960@hotmail.com (A.K. El-Hawary). 1092-9134/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.anndiagpath.2013.08.001 Contents lists available at ScienceDirect Annals of Diagnostic Pathology