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


METHODS
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(+)).


RESULTS
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.


CONCLUSIONS
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.
Ougolkov
Andrei
A
Division of Diagnostic Molecular Oncology, Cancer Research Institute, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan.
Yamashita
Kaname
K
Bilim
Vladimir
V
Takahashi
Yutaka
Y
Mai
Masayoshi
M
Minamoto
Toshinari
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000032:analysis*; D003598:Cytoskeletal Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000473:pathology; D015534:Trans-Activators / Q000032:analysis*; D051176:beta Catenin
D015820:Cadherins; D003598:Cytoskeletal Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D015534:Trans-Activators; D051176:beta Catenin; C495270:CTNNB1 protein, human