Expression of tight junction protein claudin-5 in tumor vessels and sinusoidal endothelium in patients with hepatocellular carcinoma.
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.
Sakaguchi
Takanori
T
Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan. saka1119@hama-med.ac.jp
Suzuki
Shohachi
S
Higashi
Hiroyuki
H
Inaba
Keisuke
K
Nakamura
Satoshi
S
Baba
Satoshi
S
Kato
Tomoyuki
T
Konno
Hiroyuki
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000098:blood supply* / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D062507:Claudin-5; D004730:Endothelium, Vascular / Q000737:chemistry*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000098:blood supply* / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000032:analysis*; D008875:Middle Aged
D018952:Antigens, CD34; C107466:CLDN5 protein, human; D062507:Claudin-5; D008565:Membrane Proteins