Tumor metastasis depends on cell adhesiveness, motility and deformability, resulting from quantitative alterations and rearrangement of various actin-binding cytoskeletal components, such as
cortactin and
fascin. To clarify the involvement of
cortactin and
fascin expression in
tumorigenesis and progression of gastric
carcinoma, we performed immunohistochemistry (IHC) on tissue microarray containing gastric
carcinomas,
adenomas and adjacent non-neoplastic mucosa (ANNM) using the
antibodies against
cortactin (Ab-466, -421) and
fascin as well as a comparison of their expression with clinicopathological parameters of the
tumors. Gastric
carcinoma cell lines MKN28, AGS, MKN45, KATO-III and HGC-27 were studied for both
proteins by IHC. Cortactin-466 was found to be highly expressed in
adenoma, compared with ANNMs and
carcinoma (p<0.05), and more frequently in ANNMs than in
carcinoma (p<0.05). Cortactin-421 expression was higher in gastric
carcinomas than in
adenoma and ANNMs (p<0.05). There was increased
fascin expression in gastric
carcinoma and
adenoma than in ANNMs (p<0.05). Most of the gastric
carcinoma cell lines showed expression of
cortactin and
fascin at different levels. Cortactin-466 expression was inversely correlated with
tumor size, depth of invasion, lymphatic and venous invasion,
lymph node metastasis and UICC staging (p<0.05). The converse was observed for cortactin-421 and
fascin (p<0.05). There was stronger positivity of both cortactins in intestinal- versus diffuse-type
carcinomas (p<0.05). Univariate analysis indicated the cumulative survival rate of patients with positive cortactin-466 expression to be higher than without its expression even stratified according to the depth of invasion (p<0.05). However, it was the converse for
fascin (p<0.05). Multivariate analysis showed that age, depth of invasion, lymphatic invasion,
lymph node metastasis, UICC staging and Lauren's classification were independent prognostic factors for
carcinomas (p<0.05). It was suggested that aberrant expression of
cortactin and
fascin possibly contributes to the pathogenesis, growth, invasion and
metastasis of gastric
carcinomas. Thus, they may be objective and effective markers to indicate the pathobiological behaviors and prognosis of gastric
carcinomas.