Synemin expression is widespread in liver fibrosis and is induced in proliferating and malignant biliary epithelial cells

The expression profile of intermediate filament proteins provides valuable information on the differentiation of specific cell populations and their contributions to disease. Synemin is one of the few intermediate filament proteins whose expression pattern during pathological situations is poorly characterized. We conducted a systematic immunohistochemical investigation of synemin expression in human liver diseases. In normal liver and in the early prefibrotic phase of chronic viral hepatitis or steatohepatitis, synemin was localized in hepatic stellate cells (HSCs) and vascular cells. Fibrotic or cirrhotic liver disease promoted intense synemin staining of HSCs in parenchymal and fibrous zones. In portal tract fibroblasts, synemin expression was rare under normal conditions but was widespread in severe inflammatory diseases associated with portal expansion, consistent with the notion that some fibrotic reactions involve HSCs, whereas others involve both HSCs and portal fibroblasts. Most sinusoidal endothelial cells were synemin negative in normal liver but were positive in hepatocellular carcinomas. Synemin was also expressed in the epithelial component of the ductular reaction in various liver diseases and in cholangiocarcinoma cells but not in hepatocellular carcinoma cells. Myofibroblasts in stromal reaction to carcinomas were synemin positive. Thus, synemin helps delineate different types of liver fibrotic reactions and provides a marker for sinusoidal capillarization and for proliferating biliary epithelial and cholangiocarcinoma cells.