Reply to Liver‐intestine cadherin predicts microvascular invasion and poor prognosis of hepatitis B virus‐positive hepatocellular carcinoma

Abstract

We thank Drs. Takamura and Aoyagi for their comments and interest in our article published in Cancer regarding the expression and prognostic value of liver-intestine cadherin (LI-cadherin) in hepatocellular carcinoma (HCC).1 In our article, we demonstrated that overexpression of LI-cadherin, a transmembrane protein, was presented in a cytoplasmic pattern, and it was associated with vascular invasion and poor prognosis in patients with HCC.1 Drs. Takamura and Aoyagi raised an important concern regarding the cellular localization of LI-cadherin and its corresponding prognostic significance in HCC. LI-cadherin is localized on the basolateral surface of rat hepatocytes by immunostaining, but it is undetectable in the human adult liver.2 To the best of our knowledge, positive membranous staining of LI-cadherin has been demonstrated in some human tumors in only a few studies published to date.3, 4 However, in HCC, we found that LI-cadherin was predominately overexpressed in the cytoplasm instead of the cellular membrane, which was compatible with the findings of other reports.5 In our study, a small portion of hepatitis B virus-related HCC specimens (25 of 255) possessed positive membranous LI-cadherin expression and, moreover, membranous staining was only detected in cytoplasm-positive cases. It is difficult to analyze the membranous-positive cases separately in this context. It appears that alteration of adhesion molecule expression and localization is a common event in HCC.6 Cell polarity and tissue architecture usually can be lost in hepatic carcinogenesis, which may explain at least in part the abnormal cellular distribution and expression of LI-cadherin in HCC. Furthermore, it also appears that LI-cadherin may be associated with some unknown molecular mechanisms in hepatic carcinogenesis and HCC progression, which is responsible for the cytoplasmic distribution. In conclusion, LI-cadherin has been demonstrated to be a novel biomarker and promising therapeutic target in HCC, although the mechanism still needs to be elucidated. Ying–Hong Shi MD*, Zhen–Bin Ding MD*, Jia Fan MD* , * Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.