Arp2/3 Overexpression Contributed to Pathogenesis, Growth and Invasion of Gastric Carcinoma

Abstract

Background: Tumor metastasis depends on cell adhesion, motility and deformability, resulting from quantitative alterations and rearrangement of actin-related protein (Arp) 2 and 3. The aim of this study was to clarify the roles of both molecules in tumorigenesis and progression of gastric carcinomas. Patients and Methods: Immunohistochemistry (IHC) was employed on tissue microarray containing gastric carcinomas, adjacent metaplasia and gastritis using antibodies against Arp2 and Arp3 with a comparison of their expression with clinicopathological parameters of carcinomas. Gastric carcinoma cell lines (MKN28, AGS, MKN45, KATO-III and HGC-27) were studied for Arp2 and Arp3 protein by IHC. Results: Both proteins were expressed at low levels in gastritis compared with carcinomas (p<0.05). Arp2 was more frequently expressed in intestinal metaplasia than in carcinoma and gastritis (p<0.05). Most gastric carcinoma cell lines showed expression at different levels. Expression was positively correlated with tumor size, depth of invasion, venous invasion, Union Internationale Contre le Cancer (UICC) staging and expression of cortactin or fascin (p<0.05), but not with age, sex, lymphatic invasion or lymph node metastasis (p>0.05). There was stronger positivity of Arp3 in intestinal- than diffuse-type carcinomas (p<0.05). A positive relationship between Arp2 and Arp3 proteins was noted (p<0.05). Univariate analysis indicated that the cumulative survival rate of patients with positive Arp2 or Arp3 expression was not different from those without their expression (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). Conclusion: Aberrant expression of Arp2 and Arp3 is possibly involved in pathogenesis, growth, invasion and progression of gastric carcinomas. Distinct Arp3 expression underlies the molecular mechanisms for the differentiation of intestinal- and diffuse-type carcinomas. They were considered as objective and effective markers to indicate the pathobiological behaviors of gastric carcinomas.