The Expression Of Ep-CAM In The Tissue And Serum Of Patients With Different Esophageal Mucous Membrane Diseases

Objective: Although surgical treatment with adjuvant chemo-radiotherapy has been employed in patients with esophageal carcinoma, the long-term survival is still disappointing, because the 5-year survival rate is less than 30%. Ep-CAM is a 40-kDa typeâ… transmembrane glycoprotein encoded by tumor-associated calcium signal transducer 1(TACSTD1) gene. Ep-CAM is a group of Ca2+-independent intercellular adhesion molecules on cell surface, which mediates intercellular and cell-extracellular matrix adhesion. It is closely related to tumorous generation, development and metastasis. It is reported abroad that the penetrating research on Ep-CAM was higlighted mainly on the breast cancer, colon carcinoma and lung cancer. There was a few researches on squamous carcnoma of the esophagus. The purpose of study is to investigate the expression level of Ep-CAM in the normal mucous membrane of esophagus, hyperplasia mucous membrane of esophagus and esophageal squamous cell carcinoma as well as the level of Ep-CAM expression in the serum in order to reach the early diagnosis and treatment of esophageal cancer.Methods: The samples were obtained from the patients in the Department of Thoracic Surgery, Forth Hospital of HeBei Medical University and Ci County, Hebei Province. There were 25 patients who ever underwent the operation for cancer among 32 patients with esophageal carcinoma. Twenty-eight patients with esophageal atypical hyperplasia were selected and their samples were obtained by biopsy. Ten specimens of far-end of resected esophageal cancer were selected as normal controls. These tissues proved normal esophageal mucosa by pathologic diagnosis. The serum of patients with esophageal cancer was collected 1 day before operation and 7 days after operation when they could intake food. The normal serum was taken from 11 healthy blood donors.Immunohistochemistry was used to examine the expression level of epithelial cellular adhesion molecule (Ep-CAM) in the normal mucous membrane of esophagus, hyperplasia mucous membrane of esophagus and esophageal squamous cell carcinoma. The Dako scoring system has a scale from 0 - 3+: 0, no staining or 10% or less of the tumor cells show any level of positive staining; 1+, a faint membrane staining is detected in more than 10% of the tumor cells or the cells are only stained in part of their membrane; 2+, weak to moderate staining of the entire membrane is observed in more than 10% of the tumor cells; 3+, strong staining of the entire membrane in more than 10% of the tumor cells.ELISA was used to examine the expression level of Ep-CAM in the sera of the patients with esophageal cancer or esophageal atypical hyperplasia. Evaluation of results: Subtract the average zero standard optical density to the readings for each standard, control, and sample. Create a standard curve by plotting the mean absorbance for each standard on the y-axis against the concentration on the x-axis and draw a best fit curve through the points on the graph. The data may be linearized by plotting the log of the Ep-CAM concentrations versus the log of the O.D. and the best fit line can be determined by regression analysis. This procedure will produce an adequate but less precise fit of the data. If samples have been diluted, the concentration read from the standard curve must be multiplied by the dilution factor. We use variance analysis or t test to the data with SPSS11.0.Results: 1. Expression of Ep-CAM in the normal mucous membrane of esophagus, hyperplasia mucous membrane of esophagus and esophageal squamous cell carcinoma: The negative expression of Ep-CAM existed in normal esophageal mucosa. Highly positive staining for Ep-CAM was found in primary tumor specimens and esophageal atypical hyperplasia. Ep-CAM expression was observed in 42.9%(12/18) of hyperplasia mucous membrane of esophagus and 96%(24/25) of cellular membrane of esophageal squamous cell carcinoma. There was significant difference among three groups (P<0.05). 2 Expression of Ep-CAM in serum of normal esophageal, atypical hyperplasia and esophageal cancer: There was significant difference in the expression level of Ep-CAM in serum of patients with nomal esophageal mucosa, atypical hyperplasia and esophageal cancer (P=0.01). The highest expression of Ep-CAM was detected in serum of esophageal cancer, and then moderate expression of Ep-CAM in serum of atypical hyperplasia, mild expression of Ep-CAM in serum of nomal mucosa. 3 Expression of Ep-CAM in different level of esophageal atypical hyperplasia: The Ep-CAM expression level of esophageal atypical hyperplasia in moderate or severe group was higher than that in mild group (P=0.038). There was no significant difference between the severe atypical hyperplasia and the moderate atypical hyperplasia of esophagus (P>0.05). 4 The relation between the expression level of Ep-CAM in serum and pathology charact of esophageal cancer: The expression level of Ep-CAM was not related to tumor scale, tumor invading depth and tumor differentiation (P>0.05). But its expression level was obviously associated with the lymph node metastasis (P=0.006). 5 The expression level of Ep-CAM in serum of esophageal cancer before and after operation: The expression level of Ep-CAM in serum of esophageal cancer significantly was reduced after operation (P<0.001). It almost reached normal level 7 days after operation.Conclusions: 1 Expression of Ep-CAM occurs in the esophageal mucosa and serum in lesion of early stage. 2 Ep-CAM is expressed grandiently in different grade and in different stage of esophageal mucous diseases. 3 Ep-CAM is obviously associated with the metastases of esophageal cancer and not associated with other pathologic characteristics. 4 Expression of Ep-CAM reduces significantly after operation and it can be used as a marker to monitor esophageal cancer.