Expression And Clinical Significiance Of Ezrin, CD44v6 In The Gastric Cacinoma

Objective:The Ezrin protein is a member of the Ezrin,Radixin,Moesin(ERM) proteins family that are proposed to act as linkers between the cytoskeleton and plasma membrane.Ezrin is a cytoplasmic protein enriched in microvilli and other cell surface structures.It resides on chromosome 6q25-q26.Its NH2-terminal domain is associated with the plasma membrane and the COOH-terminal domain with the cytoskeleton.Ezrin regulates cell-cell and cell-matrix interactions playing a role in the regulation of cellular adhesion,movement and morphology in epithelia.Ezrin serves as a tyrosine kinase substrate,and is phosphorylated in epidermal growth factor-stimulated cells.Ezrin is highly expressed in several types of human cancers.The CD44 gene resides on chromosome 11p13,and is known to be composed of at least 19-20 exons.As the main variant of CD44,CD44v6 is a kind of cell-surface adhesion molecule,which is important in cell-cell and cell-matrix adhesion.It could increase the metastatic potential of a tumor by facilitating the expansion of malignant cells into the draining lymph nodes.Recent studies have discovered that over expression of CD44v6 plays an important role in the growth,invasion,and metastasis of several kind of tumors such as colon cancer,breast cancer,and lung cancer..Even though it was shown that Ezrin and CD44v6 are essential for the carcinogenesis,progression and metastasis of several types of cancers,their expressions in gastric carcinoma were not analyzed so far,especially their correlations.This study was initiated to define the relationship between the expression of Ezrin and CD44v6 in gastric carcinoma and clinicopathological parameters.Methods:The study population consisted of 53 patients(31 men and 22 women,average 55.4,ranged from 28 to 82 years),diagnosed with gastric carcinoma and 20 with normal gastric mucosa in the Nanjing General Hospital of Nanjing Military Command,between 2005 and 2006.Tissue specimens were taken from operation,and all these specimens were fixed with 10%formalin and embedded in paraffin,and cut into 4μm serial sections.Standard Envision immunohistochemistry was performed using a mouse monoclonal antibody against Ezrin and CD44v6(Maxim IHC World,Fuzhou) at a dilution of 1:200.The intensity of Ezrin staining was scored as the percentage of positive tumor cells in relation to the total number cells according to Mathew's scale.(-):no staining; (+):＜50%cells staining;(++):≥50%cells staining.Membrane staining for CD44v6 was calculated as the percentage of positive tumor cells in relation to the total number cells using semiquantitative scale as follows:0=no staining;1=staining of 1-20%of cells;2=staining of 21-50%of cells; and 3=staining of 51-100%of cells.Staining intensity was scored as absent(-);weak/moderate(+);and intense(++).All statistical analyses were carried out using SPSSv.11.Categorical variables were expressed in percentages and compared using x~2 test.The correlation between Ezrin and CD44v6 was compared using Spearsman's correlation analyse.Statistical significance was accepted at P＜0.05. Results.1,The positive expression rates of Ezrin in gastric carcinoma and normal gastric mucosa were 56.6%and 30%.While the positive expression rates of CD44v6 in gastric carcinoma was 58.5%and no expression in normal gastric mucosa.2,The expression of Ezrin was correlated to differentiation(P＜0.05),and clinical stage,lymph node metastasis and metastasis in the distance(P＜0.01).The expression of CD44v6 was correlated to clinical stage,lymph node metastasis and metastasis in the distance(P＜0.01),but not to differentiation(P＞0.05).3,The expression of Ezrin was positively correlated with that of CD44v6 in gastric carcinoma(r_s=0.740,P＜0.01).Conclusion:The high expression of Ezrin and CD44v6 were correlated to the clinical stage,lymph node metastasis and metastasis in the distance.They might be served as an important parameter for determining tumor biological behavior.It is useful to forecast metastasis and prognosis of gastric carcinoma by combined examine.