Immunohistochemical localization of CEA, CA19-9 and DU-PAN-2 in hepatitis C virus-infected liver tissues

Abstract

Aims: We investigated expression of CEA, CA19-9 and DU-PAN-2 in liver tissues of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma, measuring their serum value to clarify their clinical significance, and proliferating cell nuclear antigen (PCNA) was assessed in serial sections to determine whether expression of these molecules in chronic liver disease was related to regeneration of biliary ducts.

Methods and results: Liver tissues were biopsied under peritoneoscopy or echo-guidance and resected surgically among 63 patients with anti-hepatitis C virus-positive sera. There were 26 cases of chronic hepatitis, 21 cases of liver cirrhosis and 16 cases of hepatocellular carcinoma (four cases of mixed type). They were simultaneously used for immunocytochemistry for CEA, CA19-9 and DU-PAN-2, and PCNA was demonstrated in serial liver tissues by immunohistochemistry. Serum CEA, CA19-9 and DU-PAN-2 were measured by radioimmunoassay or enzyme immunoassay. In chronic hepatitis and liver cirrhosis CEA immunoreactivity was seen on membranes facing bile canaliculi and in bile ductules. Both CA19-9 and DU-PAN-2 immunoreactivity were observed in bile ductules in chronic hepatitis liver cirrhosis and non-neoplastic areas surrounding hepatocellular carcinoma, and CA19-9 was also present in interlobular bile ducts. PCNA immunoreactivity was not detected in marker-positive bile ductules or interlobular bile ducts. In hepatocellular carcinoma CEA immunoreactivity was seen on membrane facing dilated bile canaliculi in glandular structures, and CEA, CA19-9 and DU-PAN-2 immunoreactivity was observed in cholangiolar areas in mixed type of hepatocellular carcinoma.

Conclusions: CEA in chronic hepatitis and liver cirrhosis is expressed not only in bile ductules but also on membrane facing bile canaliculi, and both CA19-9 and DU-PAN-2 were seen in different levels of biliary ducts. These molecules were expressed in bile ductules in surrounding non-neoplastic areas of hepatocellular carcinoma, and their expression was not associated with regeneration of biliary ducts. CEA expression was present in the trabecular type of hepatocellular carcinoma, and CA19-9 and DU-PAN-2 were observed in cholangiolar areas in mixed type of hepatocellular carcinoma.