Aberrant expression of cortactin and fascin are effective markers for pathogenesis, invasion, metastasis and prognosis of gastric carcinomas

Abstract

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.