Loss of Claudin-1 Expression Correlates with Malignancy of Hepatocellular Carcinoma

Background

The prognosis for the hepatocellular carcinoma (HCC) patient is affected by invasion and metastases. The attenuated expression of adherens junction protein epithelial-cadherin (E-cad) correlates with a more malignant potential in HCC. However, the potential of the claudin (CL) family of tight junctional proteins for HCC prognosis has remained unrecognized.

Materials and methods

We immunohistochemically examined the expression of CL-1 and E-cad in resected specimens from 55 HCC cases. The percentage of CL-1- or E-cad-positive cells was counted in HCC cells and the surrounding hepatocytes and scored as 0 (0%), 1 (1–33%), 2 (34–66%), and 3 (67–100%). The expression of CL-1 or E-cad was considered “preserved” if the score in HCC was equal to or more than that in the surrounding hepatocytes, and “attenuated” if not so.

Results

In nontumorous tissue, CL-1 and E-cad were observed at the lateral surface of hepatocytes and biliary epithelial cells. In well-differentiated HCCs, the expression of CL-1 and E-cad was preserved in 12 of 14 cases. In poorly differentiated HCCs, E-cad expression was preserved in 9 of 18 cases, while CL-1 expression was preserved in only 4 cases (P < 0.01 versus well-differentiated HCCs). HCCs with portal invasion showed significantly attenuated CL-1 expression than those without portal invasion (P < 0.05). The survival rate after hepatectomy for HCC with attenuated CL-1 expression was significantly lower than that for HCC with preserved CL-1 expression.

Conclusions

Attenuated expression of CL-1 closely correlates with the dedifferentiation and portal invasion of HCC. Down-regulated CL-1 expression may serve as a potential marker for a poor prognosis in HCC.

Key Words: hepatocellular carcinoma, tight junction, claudin, adherens junction, E-cadherin, hepatectomy