The Expression Of S100A4 Protein, E-Cadherin And Nm23 Protein In Cardiac Carcinoma And Their Prognostic Significance

Background and objectiveCardiac Carcinoma is one of the highest incidences of malignant tumors in Chaoshan region. One of important factors affected the prognosis is the metastasis of cardiac carcinoma. For predicting the postoperative outcome of patients, it is very considerable to search some proteins correlating with cardiac carcinoma metastasis and prognosis.A large number of studies confirm that many of the genes and their products involved in the tumor invasion and metastasis process. As a metastasis-associated gene, the over expression of S100A4 protein can promote tumor metastasis and prognosticate a poor outcome. E-Cadherin is a calcium-dependent cell-cell adhesion molecule, whose reduced expression occurs in a variety of human tumors and resulted in a shot survival period after operation. The nm23 protein is detected in many tumors, some of which show less invasive and metastatic feature. It is reported that nm23 gene is an antimetastatic gene. To further clarify the relationship among cardiac carcinoma invasion, metastasis and prognosis, we examined S100A4 protein, E-Cadherin and nm23 protein by immunohistochemistry in specimens of patients followed-up with cardiac carcinoma and analyzed the correlation of their expression, the relationship between clinicopathological parameters and their expression, the influence on the prognosis by their expression in order to provide a theoretical basis for predicting the prognosis of cardiac carcinoma.MaterialsWe collected resection specimens from 133 patients with gastric cardiac carcinoma from October 2000 to October 2002 who had underwent curative resection in Cancer Hospital of Shantou University Medical College. 126 cases of 133 patients were followed-up for no less than 5 years. In contrast, the others were less than 5 years. In all, 5-year follow-up was 94.7%. Normal cardia specimens resected from 10 cases of non-cardia diseases autopsy.MethodsWe detected the expression of S100A4 protein, E-Cadherin and nm23 protein in the paraffin sections by immunohistochemistry called Envision Labelled Peroxidase System Two-Step Method. And then, the sections were taken five images randomly using Leica DMRXA2 Almighty microscope and Leica IM50 image acquisition system. Finally, we used Image-Pro ? Plus 6.0 image analysis system to measure the mean optical density (MOD) of protein immunoprecipitates in the images.Statistical analysisWe analyzed the data by using SPSS 13.0 statistical package. The differences of mean were analyzed by t-test and one-way ANOVA. The correlation was analyzed by Pearson correlation analysis. Univariate analysis (Kaplan-Meier) was used to determine the prognostic value of the protein expression on overall survival and disease free survival. For those statistically significant factors in univariate analysis, a multivariate analysis (Cox proportional hazard model) was performed to explore the independent prognostic factors. Statistical significance was defined as by p<0.05.Results1. The expression of S100A4 protein in cardiac carcinoma was higher than that in normal cardia (p<0.05). In cardiac carcinoma, S100A4 expression negatively correlated with histological type (p<0.05), but wih clinical TNM stage, T stage and N stage positively (p<0.05). S100A4 expression did not correlate wih the clinicopathological parameters involved sex, age, tumor size and macroscopic type (p>0.05). In univariate analysis (Kaplan-Meier), the OSR and DFSR of the low group expressed S100A4 protein were higher than those of the high expression group (p<0.05), respectively.2. The expression of E-Cadherin in normal cardia was higher than that in cardiac carcinoma (p<0.05). In cardiac carcinoma, the E-Cadherin expression correlated with histological type positively (p<0.05), but with clinical TNM stage, T stage and N stage negatively (p<0.05). E-Cadherin expression did not correlate wih the clinicopathological parameters involved sex, tumor size and macroscopic type (p>0.05). In univariate analysis (Kaplan-Meier), the OSR and DFSR of the high group expressed E-Cadherin were higher than those of the low expression group (p<0.05), respectively.3. The expression of nm23 protein in normal cardia was higher than that in cardiac carcinoma (p<0.05). nm23 expression did not correlate wih the clinicopathological parameters involved sex, age, tumor size, macroscopic type, histological type, clinical TNM stage, T stage and N stage (p>0.05).In univariate analysis (Kaplan-Meier), the OSR and DFSR of the high group expressed nm23 protein was higher than that of the low expression group in tendency, but the differences had no statistical significance (p>0.05).4. In cardiac carcinoma, the Coefficient of correlation between S100A4 protein expression with E-Cadherin and nm23 protein was negative, respectively (p<0.05). But between the E-Cadherin and nm23 protein, It was no statistical significance (p>0.05).5. The patients with high expression of E-Cadherin/low expression of S100A4 protein tumors had the best survival than the other three groups. In contrast, the patients with low expression of E-Cadherin/high expression of S100 A4 protein tumors had the poorest survival.6. The analysis of Cox proportional hazard model indicated that sex, T stage, N stage and E-Cadherin were independent prognostic factors for overall survival. Conclusion1. In cardiac carcinoma, S100A4 expression negatively correlated with histological type (p<0.05), but will clinical TNM stage, T stage and N stage positively (p<0.05). It indicated that S100A4 protein promoted the invasion and metastasis of the tumor. In contrast, E-Cadherin expression correlated with histological type positively (p<0.05), but with clinical TNM stage, T stage and N stage negatively (p<0.05). It indicated that E-Cadherin suppressed the invasion and metastasis of the tumor.2. In cardiac carcinoma, overexpression of S100A4 protein negatively correlated with reduced expression of E-Cadherin, It indicated that they played roles conversely in the invasive progression and metastasis of the tumor.3. Survival analysis displayed that the patients with high expression of E-Cadherin/lowexpression of S100A4 protein tumors had the best survival. Inversely, the patients with lowexpression of E-Cadherin/high expression of S100A4 protein tumors had the poorest survival.It indicated that detection and analysis of E-cadherin and S100 A4 protein together maypredict the prognosis of patients with cardiac carcinoma.