Ezrin expression and its phosphorylation in gastric carcinoma with lymphoid stroma and Epstein-Barr virus infection

Abstract

Abstract. Gastric carcinoma with lymphoid stroma (GCLS) is a unique variant of gastric carcinoma that represents prominent lymphocytic infiltration and is correlated with Epstein-Barr virus (EBV) infection. Ezrin expression and activation are crucial in tumor metastasis and induce cell migration of EBV-related nasopharyngeal carcinomas. Using immunohistochemical methods, the expression of total and phosphorylated ezrin (p-ezrin), Thr567, was examined in 104 GCLS cases, including 78 EBV-positive and 26 EBV-negative cases, as well as 29 non-GCLS cases. Positive ezrin expression was detected to be at markedly higher levels in GCLS compared to non-GCLS (P<0.0001). Furthermore, ezrin expression was detected to be at higher levels in EBV-positive compared to EBV-negative GCLS (P=0.0294). High expression of p-ezrin in GCLS was associated with positive lymph node metastasis (P=0.0187). In summary, these results demonstrated that ezrin overexpression is correlated with the histologic characteristics of GCLS and EBV infection. Phosphorylation of ezrin may, therefore, contribute to lymph node metastasis in GCLS.

Clinicopathological Features and Prognostic Implication of Gastric Carcinoma with Lymphoid Stroma

“…We found higher EBV positivity in GCLS than in non-GCLS (72.3% vs. 6.4%; P < 0.001 in the metaregression test). The positive rates of EBV in non-GCLS varied from 0% to 19% among eligible studies [ 5 , 32 ]. However, because the EBV positive rate was not 100%, the comparison of clinicopathological characteristics between EBV positive (EBVaGCLS) and negative GCLSs (non-EBVaGCLS) can be useful in understanding GCLS.…”

Clinical application of early gastric carcinoma with lymphoid stroma based on lymph node metastasis status

“…It is known that GCLS has a lower risk of LNM than other subtypes of gastric cancer [14]. Also, in a recent study of ezrin targeting, it was found that ezrin expression is correlated with EBV-positive GCLS, and that the phosphorylation of ezrin is essential in the LNM of GCLS [19]. However, despite its low risk of LNM, GCLS can be classified as undifferentiated cancer due to its undifferentiated histological features and indistinct histological classification.…”

Features of Gastric Carcinoma With Lymphoid Stroma Associated With Epstein-Barr Virus

“…Advances of molecular biology facilitated comprehensive molecular characterization of EBV-associated gastric cancer, and showed that EBV infection creates alterations in genes, gene expression, and methylation of the infected host cell, and is associated strongly with phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutation, extreme DNA hypermethylation, ezrin expression, and immune cell signaling in gastric cancer carcinogenesis. [16][17][18] In addition, recent study of targeting for ezrin showed that ezrin expression is correlated with EBV-positive GCLS and the phosphorylation of ezrin is essential in the tumor metastasis of GCLS. 18 However, to date, whether EBV infection influences the prognosis of gastric cancer remains controversial.…”

“…[16][17][18] In addition, recent study of targeting for ezrin showed that ezrin expression is correlated with EBV-positive GCLS and the phosphorylation of ezrin is essential in the tumor metastasis of GCLS. 18 However, to date, whether EBV infection influences the prognosis of gastric cancer remains controversial. 4,5,19,20 Some previous studies have reported that EBV-positive gastric cancer does not show a different prognosis than EBV-negative gastric cancer.…”