Expression Of Ep-CAM And 4D10 In Sera Of Gastrointestinal Malignancies And Clinical Values

Background: Gastric carcinoma (GC) and Colorectal carcinoma (CRC) are malignant tumors which frequently occurred in gastrointestinal system and their morbidity and mortality have been rising in resent years. It is important to detect and diagnose in nonage in order to prevent and cure GC and CRC in time. Resection remains the major treatment for GC and CRC at present, which assisted with combined therapy including chemotherapy, radiotherapy, immunotherapy, etc. Earlier diagnosis and surgery are key factors in decreasing morbidity and prolonging the life of patients with GC and CRC.Epithelial cell adhesion molecule (Ep-CAM) is a kind of transmembrane glycoprotein which was negatively or weakly expressed in normal epithelial cells and frequently overexpressed in epithelial carcinomas such as gastric carcinoma, colorectal carcinoma, breast cancer, head and neck carcinoma and hepatoma,etc. It was reported that Ep-CAM mediates calcium-independent homophilic adhesion and correlates with cellular proliferation, invasion, de-differentiation as well as migration. We have studied the expression of Ep-CAM in GC and CRC tissues and adjacent paracancerous tissues and the results showed that the expression of Ep-CAM in GC and CRC tissues were higher than that of the latter (p<0.01). At present, there are few studies about the Ep-CAM quantitive expression in cancer sera and its clinical significance was reported.4D10 was a tumor associated antigen obtained from cultured colon cancer cell line LOVO, which can react to the colon cancer but very little or not to normal tissue and other caner tissues. The purified antigen was identified by SDS-PAGE and Western blot analyse. The antigen 4D10 was a heterodimer composed of two subunits with relative molecular mass (Mr) of 3×10~3 and 35×10~3 respectively.Objective: 1.To investigate the expression of Ep-CAM and 4D10 in sera of GC and CRC, 2. Expression of Ep-CAM and 4D10 in sera of gastrointestinal benign disease and health adults were also detected and compraed with that of GC and CRC. 3. To study the correlation of the expression of Ep-CAM and 4D10 in sera of GC and CRC with clinicopatholgic characteristics of tumors. 4. The values of combined detection of Ep-CAM and 4D10 in GC and CRC and to explore the feasibility of Ep-CAM and 4D10 as tumor markers for GC and CRC.Methods: 53 primary gastric carcinoma sera specimens and 40 colorectal carcinoma sera specimens which obtained from patients underwent surgery and confirmed by pathology were included in the study group. 30 sera specimens of gastrointestinal benign disease and 50 sera specimens from health adults which offered by Central Blood Bank of Red Cross of Anhui province were included in control group. Double antibody sandwich ELISA was used to examine the expression of Ep-CAM and 4D10 in all sera specimens, and the relation of expression of Ep-CAM and 4D10 between study group and control group was analyzed. Furthermore, the expression of Ep-CAM and 4D10 in study group was also analyzed with regard to clinicopathologic characteristics. The results demonstrated as optical density (Ep-CAM OD). Relation between the expression of Ep-CAM and that of 4D10 was also analyzed.Results: 1. The Ep-CAM OD of GC group was 0.550±0.1109, the Ep-CAM OD of CRC group was 0.643±0.0573, the Ep-CAM OD of gastrointestinal benign disease group was 0.248±0.0411 and the Ep-CAM OD of health adults group was 0.247±0.0152. The Ep-CAM OD in study group was significantly higher than control group (P<0.01).2. The 4D10 OD of GC group was 0.558±0.1197, the 4D10 OD of CRC group was 0.741±0.1201, the 4D10 OD of gastrointestinal benign disease group was 0.331±0.0151 and the OD of health adults group was 0.247±0.0152. The 4D10 OD in study group was significantly higher than control group (P<0.01).3. High-level expression of Ep-CAM and 4D10 were observed in gastric carcinoma in TNMⅠ,Ⅱstage and in colorectal carcinoma in Dukes A,B stage. High-level expression of Ep-CAM and 4D10 were also observed in tumor size less than 5cm and tumor infiltrate in muscular layer .The expression of Ep-CAM and 4D10 in study group increased in early period of GC and CRC and could be detected.4. Expression of Ep-CAM correlates with that of 4D10 in GC and CRC, and the early diagnosis rate of GC and CRC could be raised by combined detection with Ep-CAM and 4D10.5. Expression of Ep-CAM and 4D10 were not influenced by clinicopathological characteristic such as age, gender, pathologic type, differention and lymphoid node metastasis etc.Conclusion: 1. High-level expression of Ep-CAM and 4D10 were observed in gastric carcinoma and colorectal carcinoma, and they were involved in GC and CRC genesis and development.2. Ep-CAM and 4D10 play important roles in gastric and colorectal carcinogenesis and can be detected in early stage. They may serve as markers in the early diagnosis of gastric carcinoma and colorectal carcinoma.3. The early diagnosis rate of GC and CRC could be raised by combined detection with Ep-CAM and 4D10.4. Expression of Ep-CAM and 4D10 were not influenced by clinicopathological characteristic such as age, gender, pathologic type, differention and lymphoid node metastasis, etc. Ep-CAM and 4D10 may be independent inflence factors in the GC and CRC carcinogenesis and development.