Expression Of E-CD And Snail In Colorectal Cancer

Introduction:Colorectal cancer is one of the commonest tumors in China, and its morbidity is still increasing. The 5-year survival rate after curative resection is about 50-60%, although the operation-based comprehensive therapies have greatly improved the prognosis of colorectal cancer in recen(?) years. The two major features of malignant rumors are infiltration and metastasis, which are the direct causes of death of post-operative patients with cancer. Elucidating the molecular biological events which influence the prognosis of colorectal cancer, predicting the infiltrated and metastasis tendency of colorectal cancer, which can indicate to use more effective comprehensive therapies, and reduce the post-operative recurrence or metastasis.Infiltration of tumors is a process of interaction between tumor cells and extracellular matrix. It includes three steps which are cell adhesion, matrix degradation and cell migration. Disruption of cell-cell adhesion has been considered the first step in the tumor metastasis. The cell adhesion molecules included integrins, CD44, cadherins, immunoglobulin superfamily, selections, etc. As one of the cell adhesion molecules, E-CD is a transmembrane glycoprotein that is responsible for calcium-dependent intercellular adhesion by hemophilic interaction. It is expressed in the epithelium and placenta where is maintains the epithelial structure and polarity.E-CD is mainly distributed at the cell border and in particular at cell-cell adhesion areas. Cells without E-CD expression can not aggregate or adhere to each other. It has been demonstrated the existence of lower E-CD expression in may human malignant tumors, and that there was a significant relationship between lower E-CD expression and infiltration, metastasis or prognosis of malignant tumors. Snail is Zinc Finger transcription factor .It can regulate the function of E-CD and inhibit the expression of E-CD, through the Zinc Finger region combined with CANNTG sequence of E-CD promoter. Snail is an important Regulator in tumor infiltration. It has negative correlation with the expression of E-CD. It can promote the infiltration and metastasis of tumor. Many studies in vivo have demonstrated that the expression of Snail is increased in many human malignant tumors, and the strong expression of snail has significant correlation with poor clinic and pathological features of tumor. However, studies on the relationship between E-CD and Snail expression in colorectal cancer and tumor invasion, metastasis and prognosis has not been reported in domestic documents to the date time.In the present study, we investigated the expression of E-CD and Snail in colorectal cancer tissues by using immunohistochemical method (EnVisiion) to evaluate the relationship between the expression of E-CD or Snail and infiltration, metastasis or prognosis in colorectal cancer. We hope to provide useful biological indicators for predicting prognosis of colorectal cancer.142 Patients with colorectal cancer who underwent surgical resection at Zhejiang Provincial People s Hospital from January 1988 to December 2001 were admitted. A control group includes 30 normal colorectal mucosa and 30 colorectal adenomas. All cases were verified by operation and pathology. The median follow-up time was 55.04 months, with a range of 4 months to 142 months. All the specimens were fixed in 10% formalin and embedded in paraffin. Consecutive sections from each specimen were stained with hemotoxylin-eosin for evaluating pathological parameters, and with immunohistochemical technology (EnVision) for detecting the expression of E-CD and snail.SPSS-11.5 program package were used for statistical calculations. The correlation between grading of E-CD or snail expression and the various pathologic findings was analyzed by chi-square test or Fishers exact probability test or Kaplan-Meier test. The univariate survival analysis was based on the life table method with statistics by Kaplan-Meier. Multivariate survival analysis was based on Cox's regression analysis. P values < 0.05 were considered significant.Results: 1. E-CD(1) Of the 30 normal colorectal mucosa epithelium expressed E-CD, 3 (10 %) specimens expressed as moderate positive and 27 (90%) specimens as strong positive. Among 30 specimen of colorectal adenomas, 1 (3.33%) expressed as negative, 10 (33.33%) as moderate positive, 19 (63.33%) as strong positive. Among colorectal cancer, rates of negative, moderate and strongly positive expression were 21.13% (30/142), 37.32% (53/142) and 41.55% (59/142), respectively. The result indicates that expression of E-CD in colorectal cancer is lower than that in normal colorectal mucosa and colorectal adenomas. There was significant difference of E-CD expression among normal epithelium, adenomas and carcinoma (p<0.05).(2) The staining intensity of E-CD significantly correlated with differentiation, invasive depth, lymph node metastasis and Dukes' stage, but not with age, gender, tumor size and pathological types.(3) The 1-, 3- and 5-year survival rate of 30 cases with colorectal cancer that don't expressed E-CD was 86.67%, 53.33 % and 33.33 %, respectively. The 1-, 3- and 5-year survival rate of 53 cases with moderate positive expression of E-CD was 92.45%, 60.38% and 45.28%, respectively. The 1-, 3- and 5-year survival rate of 59 cases with strongly positive expression of E-CD was 100%, 76.27% and 49.15%, respectively. It indicates that negative expression of E-CD in colorectal cancer is poor prognosis (p=0.000).(4) In 45 cases with colorectal cancer of Dukes" B stage, the 1- 3- and 5-yearsurvival rate of 7 cases that don't expressed E-CD was 87.71%, 57.14% and 0 respectively, the 1-, 3- and 5-year survival rate of 38 cases with moderate and strongly positive expression of E-CD was 97.37%, 65.79% and 39.47%, respectively. The result indicates that the negative expression of E-CD in colorectal cancer of Dukes' B stage is poor prognosis (p=0.000). 2. Snail(1) Expression of Snail in normal colorectal mucosa epithelium was very weak, rate of negative, moderate and strong expression was 93.33% (28/30), 67% (2/30) and 0, respectively. Rate of negative, moderate and strong expression of Snail in colorectal adenomas was 73.33% (22/30), 26.67% (8/30) and 0, respectively. In colorectal cancer, rate of negative, moderate and strong expression of Snail was 47.89% (68/142), 42.25% (60/142) and 9.86% (14/142), respectively. The result indicates that expression of Snail in colorectal cancer is higher than that in normal colorectal mucosa and colorectal adenomas (p<0.05).(2) The staining intensity of Snail significantly correlated with differentiation, pathological types, invasive depth, venous vessel invasion, lymphatic vessel invasion, lymph node metastasis and Dukes' stage, but not with age, gender and tumor size.(3) The 1-, 3- and 5-year survival rate of 68 cases with colorectal cancer that don"t expressed Snail was 100%, 70.59% and 47.06%, respectively. The 1-, 3- and 5-year survival rate of 60 cases with moderate positive expression of Snail was 90%, 56.67% and 46.67%, respectively. The 1-, 3- and 5-year survival rate of 14 cases with strong positive expression of Snail was 85.71%, 50% and 21.43%, respectively. The result indicates that positive expression of Snail in colorectal cancer is poor prognosis (p=0.000).(4) In 45 cases with colorectal cancer of Dukes" B stage, the l- 3- and 5-year survival rate of 26 cases that don't expressed Snail was 100 %, 69.23% and 42.31% respectively, the 1-.3- and 5-year survival rate of 19 cases with moderate and strongly positive expression of Snail was 89.47%, 57.89% and 26.32%, respectively. The result indicates that the positive expression of Snail in colorectalcancer of Dukes' B stage is poor prognosis (p=0.000). 3. The results of multivariate survival analysis demonstrated that lymph nodemetastasis, Dukes' stage, expression of E-CD or Snail can predict survival ofpatients with colorectal cancer. Conclusion: 1 In normal colorectal mucosa, the staining intensity of E-CD is strongly ormoderate positive, however the staining intensity of Snail is mostly negative. Incolorectal cancer, expression of Snail is higher than that in normal colorectalmucosa. 2 The staining intensity of E-CD and Snail is significantly correlated with theinfiltration, metastasis and prognosis of colorectal cancer. The weak stainingintensity of E-CD or strong staining intensity of Snail indicates poor prognosis ofcolorectal cancer.3 The expression of Snail is negative correlation with that of E-CD. 4 Both the staining intensity of E-CD and Snail is an independent prognosticpredictor in patients with colorectal cancer. 5 In colorectal cancer of Dukes' B stage, the negative expression of E-CD orpositive expression of Snail is poor prognosis.