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Cellular Characterization of Multidrug Resistance P-glycoprotein, Alpha Fetoprotein, and Neovascular Endothelium-Associated Antigens in Canine Hepatocellular Carcinoma and Cirrhotic Liver

Department of Veterinary Pathobiology, Small Animal Tumor Diagnostic Center (RET, DNH, GSS, YSL, SJL, JHS) and the Departments of Veterinary Public Health (NHC), Veterinary Anatomy (JHL), Veterinary Internal Medicine (DIJ), and Veterinary Surgery (HYK), College of Veterinary Medicine, Konkuk University, Seoul, Korea

P-glycoprotein (P-gp), which is encoded by the multidrug resistance gene (MDR-1); alpha fetoprotein (AFP); and vascular endothelium-associated antigens are well-known markers for human and canine hepatic diseases. We obtained liver tissues from 5 dogs with hepatocellular carcinoma (HCC) and 12 dogs with cirrhosis, and we performed histopathologic and immunohistochemical evaluations using anti–P-gp, anti-AFP, anti-CD31, and anti-CD34 antibodies. P-gp was expressed at higher levels in HCC than in cirrhotic livers ( P < .01), and was most commonly localized in biliary canaliculi and small ductuli. AFP was localized mainly in the cytoplasm in HCC ( P < .01) and in a few cases of cirrhosis. In both HCC and cirrhosis, the AFP-positive cells were morphologically similar to normal hepatocytes and showed an even cytoplasmic distribution of AFP. The endothelial markers CD31 and CD34 were used to investigate vascular distribution. CD31 was expressed strongly in the portal area and parenchyma in HCC, but it was rarely observed in the parenchyma in cirrhosis. CD34 expression could not be detected in both HCC and cirrhosis. This study constitutes the first comprehensive study of P-gp, AFP, and endothelial markers in canine HCC and cirrhosis. The importance of these markers in HCC and cirrhosis in dogs was demonstrated and provides a more accurate basis for a definitive diagnosis of HCC and cirrhosis in dogs.

Key words: Alpha fetoprotein; dogs; hepatocellular carcinoma; immunohistochemistry; liver cirrhosis; multidrug resistance; p-glycoprotein; vascularization.

Request reprints from Dr. Jung-Hyang Sur, Department of Veterinary Pathobiology, College of Veterinary Medicine, Konkuk University, Hwayang-dong 1, KwangJin-Ku, Seoul 143-701, (Korea). E-mail: jsur{at}konkuk.ac.kr

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