Inverse expression of S100A4 and E-cadherin is associated with metastatic potential in gastric cancer

S100A4 is known to be involved in cancer cell motility by virtue of its abi lity to activate nonmuscle myosin, E-cadherin has an important role in the homophilic cell-cell adhesion and is called an invasion suppressor gene. In the current study, we investigate the histological type and metastatic pot ential of gastric cancer from the aspect of the interrelationship of E-cadh erin and S100A4 expression. Expression of E-cadherin and S100A4 in gastric cancer cell Lines, primary g astric cancers, and their normal counterparts were analyzed by reverse tran scription-PCR, Western blot, and immunohistochemical methods. S100A4 protein and E-cadherin were expressed in five of eight gastric cance r cell lines, and inverse expression of the two proteins are found in four cell lines. In the clinical specimens, E-cadherin mRNA expression in differ entiated adenocarcinomas (88%, 14 of 16) was significantly more frequent th an that in poorly differentiated adenocarcinomas (50%, 22 of 44; P = 0.015) , Western blot analysis demonstrates that S100A4 protein expression in poor ly differentiated adenocarcinomas was 1.6-fold higher than in well differen tiated adenocarcinoma, Zn-Immunohistochemically, S100A4 expression was dete cted in 51 (55%) of 92 primary gastric cancers, Reduced expression of E-cad herin in primary tumors was found in 66 (72%) of 92 tumors, S100A4 expressi on in the poorly differentiated adenocarcinomas had a strong relation to po sitive lymph node involvement or peritoneal dissemination. Reduced E-cadher in expression showed a strong relationship with positive serosal involvemen t and infiltrating type, Tumors classified as a group with reduced E-cadher in and high expression of S100A4 reveal positive peritoneal dissemination, serosal involvement, and infiltrating type in the growth pattern. Furthermo re, these tumors showed a strong correlation with the poorly differentiated adenocarcinoma, In contrast, tumors with preserved E-cadherin and low expr ession of S100A4 have a close relation to the well differentiated adenocarc inoma and a favorable prognosis. By the Cox proportional hazard model, S100 A4 and E-cadherin tissue status was judged as an independent prognostic fac tor. S100A4 and E-cadherin tissue status may be a powerful aid in evaluatin g metastatic potential or the prognosis of patients with gastric cancer.