To investigate the possible relationship between altered expression (loss o
f membranous staining or nuclear accumulation) of beta -catenin and invasio
n/metastasis in early gastric cancer (EGC), beta -catenin was detected immu
nohistochemically in 116 cases of EGC, including 86 differentiated and 30 u
ndifferentiated carcinomas. In parallel, immunohistochemical expression of
c-erbB-2 was analyzed in all EGC cases. Regardless of histological type, al
tered expression of beta -catenin was found in 47% of mucosal carcinomas an
d 89% of carcinomas with submucosal invasion (p<0.001). Of particular inter
est is that <beta>-catenin alteration was found in almost ail EGCs with lym
ph node metastasis, even though no significant statistical comparison could
be made. These results suggest that molecular changes resulting in abnorma
l beta -catenin expression participate in the process of submucosal invasio
n and metastasis. While loss of expression was preferentially observed in u
ndifferentiated EGCs, nuclear accumulation was found exclusively in 24% of
differentiated EGCs. c-erbB-2 was overexpressed in only 16% of differentiat
ed EGCs but there was no correlation between this overexpression and invasi
on or metastasis. However, it is intriguing that 12 out of 14 cases with c-
erbB-2 overexpression also showed altered beta -catenin expression, suggest
ing that both molecules are involved in the development of a certain set of
differentiated EGCs.