Expression of tight junction protein claudin-5 in tumor vessels and sinusoidal endothelium in patients with hepatocellular carcinoma.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Takanori Sakaguchi, Shohachi Suzuki, Hiroyuki Higashi, Keisuke Inaba, Satoshi Nakamura, Satoshi Baba, Tomoyuki Kato, Hiroyuki Konno
• Journal: The Journal of surgical research (J Surg Res) Vol. 147 Issue 1 Pg. 123-31 (Jun 01 2008) ISSN: 0022-4804 [Print] United States
• PMID: 17981296 (Publication Type: Journal Article)

Chemical References

• Antigens, CD34
• CLDN5 protein, human
• Claudin-5
• Membrane Proteins

Topics

• Adult
• Aged
• Aged, 80 and over
• Antigens, CD34 (analysis)
• Carcinoma, Hepatocellular (blood supply, chemistry, mortality, pathology)
• Claudin-5
• Endothelium, Vascular (chemistry)
• Female
• Humans
• Immunohistochemistry
• Liver Neoplasms (blood supply, chemistry, mortality, pathology)
• Male
• Membrane Proteins (analysis)
• Middle Aged