Altered expression of beta-catenin and c-erbB-2 in early gastric cancer.
To investigate the possible relationship between altered expression (loss of membranous staining or nuclear accumulation) of beta-catenin and invasion/metastasis in early gastric cancer (EGC), beta-catenin was detected immunohistochemically in 116 cases of EGC, including 86 differentiated and 30 undifferentiated carcinomas. In parallel, immunohistochemical expression of c-erbB-2 was analyzed in all EGC cases. Regardless of histological type, altered expression of beta-catenin was found in 47% of mucosal carcinomas and 89% of carcinomas with submucosal invasion (p<0.001). Of particular interest is that beta-catenin alteration was found in almost all EGCs with lymph node metastasis, even though no significant statistical comparison could be made. These results suggest that molecular changes resulting in abnormal beta-catenin expression participate in the process of submucosal invasion and metastasis. While loss of expression was preferentially observed in undifferentiated EGCs, nuclear accumulation was found exclusively in 24% of differentiated EGCs. c-erbB-2 was overexpressed in only 16% of differentiated EGCs but there was no correlation between this overexpression and invasion or metastasis. However, it is intriguing that 12 out of 14 cases with c-erbB-2 overexpression also showed altered beta-catenin expression, suggesting that both molecules are involved in the development of a certain set of differentiated EGCs.
Ougolkov
A
A
Division of Molecular Diagnostic Pathology, Cancer Research Institute, Kanazawa University, Ishikawa, Japan.
Mai
M
M
Takahashi
Y
Y
Omote
K
K
Bilim
V
V
Shimizu
A
A
Minamoto
T
T
D000230:Adenocarcinoma / Q000145:classification / Q000378:metabolism* / Q000556:secondary; D002288:Adenocarcinoma, Mucinous / Q000145:classification / Q000378:metabolism* / Q000556:secondary; D000231:Adenocarcinoma, Papillary / Q000145:classification / Q000378:metabolism* / Q000556:secondary; D000328:Adult; D000368:Aged; D018279:Carcinoma, Signet Ring Cell / Q000145:classification / Q000378:metabolism* / Q000556:secondary; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D015534:Trans-Activators; D051176:beta Catenin
D003598:Cytoskeletal Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D015534:Trans-Activators; D051176:beta Catenin; C495270:CTNNB1 protein, human