Annexins belong to a family of the calcium-dependent phospholipid binding p
roteins. They are also substrates of receptor tyrosine kinases. Overexpress
ion of Annexin II, which has been reported in various carcinomas, is though
t to be associated with cell proliferation, differentiation and cell-cell a
dhesion in the pathogenesis of carcinoma, but the functions of Annexins hav
e not been fully elucidated. In this study, we investigated the role of Ann
exin II (p36) and its relationship with c-erbB-2 overexpression in gastric
carcinoma. We studied Annexin II expression using Western blot analysis in
8 human gastric carcinoma cell lines and expression of Annexin II and c-erb
B-2 using, immunohistochemistry in 153 primary gastric carcinomas. Western
blot revealed that Annexin II was expressed in 8 human gastric carcinoma ce
ll lines. It was more strongly expressed in the cell membrane than in the c
ytoplasm of rumor cells in primary gastric carcinoma tissues. Thirty-three
percent of all cases were immunopositive for Annexin II, overexpression of
which was more frequent in differentiated type (p=0.0009), lymph node, meta
stasis (p=0.0147) and venous invasion (p=0.0092). Annexin II and c-erbB-2 o
verexpression were significantly correlated (p=0.0002) and patients with An
nexin II had poorer prognoses (p=0.0066). Multivariate analysis showed that
immunopositivity of both Annexin II and c-erbB-2 was an independent and po
or prognostic factor (p=0.0037). In conclusion, Annexin II was overexpresse
d in advanced gastric carcinomas and it could contribute to the progression
of gastric carcinoma.