Liver-intestine cadherin (LI-cad) is a non-classical cadherin, which is expressed during intestinal development, but absent in normal liver tissue. Our earlier investigation has detected overexpression of LI-cad in gastric adenocarcinoma and indicated its association with lymph node metastasis. Herein, we found in RT-PCR and TaqMan Q-PCR that LI-cad was identified in HCC cell lines, HuH-7, Hep-3B, and PLC/PRF/5, but not in MIHA and HepG2 non-tumorigenic cells. Immunofluorescence cytochemistry assay revealed that the Ll-cad was predominantly expressed in cytoplasm of HCC cells, contrary to that of E-cad immunostain at the plasma membrane region. By testing against 18 pairs of HCC and adjacent non-tumor tissues, 13 cases (72.2%) showed over expression of LI-cad in HCC tissues, 2 cases (11.1%) were similar, and 3 cases did not yield detectable signal. None of the 6 normal liver specimens tested was positive with LI-cad. Taken together, LI-cad could be a potential disease marker for HCC. (C) 2003 Elsevier Inc. All rights reserved.