Original ArticlesAgrin and CD34 Immunohistochemistry for the Discrimination of Benign Versus Malignant Hepatocellular LesionsTátrai, Péter, PhD* †; Somorácz, Áron, MD* †; Batmunkh, Enkhjargal, MD†; Schirmacher, Peter, MD, DSc‡; Kiss, András, MD, PhD†; Schaff, Zsuzsa, MD, DSc†; Nagy, Péter, MD, DSc*; Kovalszky, Ilona, MD, DSc*Author Information *1st Department of Pathology and Experimental Cancer Research †2nd Department of Pathology, Semmelweis University, Budapest, Hungary ‡Institute of Pathology, University Hospital, Heidelberg, Germany Supported by the grants No. 67925 and 75468 from the Hungarian Scientific Research Fund (OTKA). Correspondence: Péter Tátrai, PhD, Research fellow, 2nd Department of Pathology, Semmelweis University, 93 Üllõi út, Budapest H-1091, Hungary (e-mail: firstname.lastname@example.org). Péter Tátrai and Áron Somorácz are equal contributors. The American Journal of Surgical Pathology: June 2009 - Volume 33 - Issue 6 - p 874-885 doi: 10.1097/PAS.0b013e318194b3ea Buy Metrics Abstract Agrin is a recently identified proteoglycan component of vascular and bile duct basement membranes in the liver. The selective deposition of agrin in hepatocellular carcinoma (HCC) microvessels versus sinusoidal walls prompted us to investigate the utility of agrin immunohistochemistry (IHC) in detecting malignant hepatocellular lesions. We focused on the differential diagnostic problems often presented by hepatocellular adenomas (HCAs) and dysplastic nodules. IHC for agrin was performed on 138 formalin-fixed, paraffin-embedded surgical specimens from 93 patients, including cirrhotic liver tissues (25), focal nodular hyperplasia (10), large regenerative nodules (8), low-grade (23) and high-grade (7) dysplastic nodules, small HCC (8), HCC (27), and HCA (30). Agrin immunostaining was compared with that of CD34 and, in selected cases, to glypican-3. The combination of agrin and CD34 sensitively (0.94) and specifically (0.93) identified lesions judged previously as malignant by histology. The majority of benign lesions were clearly agrin-negative, whereas the strength and extent of agrin IHC faithfully reflected dysplasia in “atypical” HCAs and in high-grade dysplastic nodules. Malignant lesions were uniformly positive. In conclusion, as agrin is highly selective for tumor blood vessels, IHC for agrin facilitates the discrimination of benign and malignant hepatocellular lesions. Moreover, whereas glypican-3 in some HCCs may appear in few scattered cells only, agrin is diffusely deposited in virtually all malignant lesions, which may prove advantageous in the evaluation of small specimens such as core biopsies. © 2009 Lippincott Williams & Wilkins, Inc.