Expression of Tight Junction Protein Claudin-5 in Tumor Vessels and Sinusoidal Endothelium in Patients With Hepatocellular Carcinoma

Abstract

An increase of leaky vasculature is vital for the growth and metastasis of hepatocellular carcinoma (HCC). The paracellular permeability-regulating proteins in tumor vessels and adjacent sinusoids have not been studied in HCC patients. Expression of an endothelial tight junction protein claudin-5 (CL-5) and a standard endothelial marker CD34 were immunohistochemically examined in resected specimens from 51 HCC cases. The relationship between hepatitic or fibrotic grade and CL-5 expression pattern in sinusoidal endothelial cells (SECs) was evaluated in the tumor-adjacent tissues. Microvessel density (MVD) highlighted by CD34 or CL-5 was examined in tumor tissues. In the normal liver, a ubiquitous CL-5 expression was seen in SECs, the arteries, and portal veins but not in the central veins. Sinusoidal CL-5 expression was down-regulated according to the increase of hepatitic or fibrotic grade. Poor differentiation and vasculobiliary invasion were significantly associated with a lower CL-5-MVD but not CD34-MVD. By multivariate analysis, vasculobiliary invasion and lower CL-5-MVD were independent factors associated with a lower postoperative overall survival rate. Attenuated CL-5 expression in SECs may be related to SEC dysfunction in injured liver. Down-regulated CL-5 expression in tumor vessels may serve as a potential marker for poor prognosis in HCC.