Abnormal expression of E-cadherin, beta-catenin, and c-erbB-2 in advanced gastric cancer: its association with liver metastasis.

Abstract

We investigated expression of E-cadherin, beta-catenin, and c-erbB-2 in gastric cancer to identify molecular factor(s) relevant to development of liver metastasis, which is a frequent cause of mortality in gastric cancer patients. We analyzed by immunohistochemistry and compared expression patterns of E-cadherin, beta-catenin, and c-erbB-2 in the tumor between 40 cases of gastric cancer (GC) without (GC-H(-)) and 16 with concurrent liver metastasis (GC-H(+)). Loss of E-cadherin expression in the primary tumor was found in 18% of GC-H(-) and in 19% of GC-H(+). Oncogenic beta-catenin activation, represented by its nuclear translocation, was detected in 13% of GC-H(-) and in 31% of GC-H(+). There was no statistical difference in incidence of alteration in these molecules between the two groups of patients. c-erbB-2 overexpression was more frequently observed in GC-H(+) (10/16, 63%) than in GC-H(-) (5/40, 13%) while the distribution of histological types of the tumors was similar in the two groups of patients. This overexpression was also detected in metastatic liver tumors and biopsy specimens in the ten of the former group of patients. Our results strongly suggest a role of activated c-erbB-2 in the process of liver metastasis, and an importance of detection of this overexpression in biopsy specimens to identify GC patients who are at high risk of developing liver metastasis.