| Background:Gastric cancer is a common malignancy.In the past 70 years,with the boosting of medical standards and medical conditions,the incidence and mortality rate of gastric cancer have decreased significantly,but its incidence is still high in the fourth place in the world,and the gastric cancer-related mortality rate is ranked second and is only the second to lung cancer.Currently,studies have shown that the occurrence and development of gastric cancer is related to the factors such as benign chronic gastric diseases and gastric epithelium mucosae dysplasia,three kinds of heteromorphism hyperplasia,mild,moderate and severe are always occurred in most benign chronic gastric diseases'mucosa epithelium , in which heteromorphism with severe hyperplasia 75%- 80% of patients can become cancerous,so the early detection,early diagnosis and early treatment of gastric cancer namely secondary prevention is very important to the patients'prognosis.The diagnosis of gastric cancer is currently based primarily on clinical symptoms,physical signs,imageology examination and histopathological examination,and traditional detecting the tumor-related gene expression is to use large tissue section immunohistochemistry , each slice can only detect a case , not only time-consuming and reagent-quantity-using,but also the experimental conditions in different cases are difficult to keep consistent,the results are apt to produce error. However, detecting several hundred of cases through a slice,tissue microarray technology increases the detection scale and improves the detection efficency and reduces the error of different cases'immunohi- stochemistry and results.In the recent years,tumor markers'detection and application are much concerned and paid attention,especially afer AFP in hepatic cell carcinoma (HCC),PSA in prostate cancer bring unprecedented success when used in censusing the asymptomatic tumor patients,which makes the medical people in the world unremitting to find reliable tumor markers.At the present stage,the early detection,early diagnosis and early treatment of gastric cancer mainly depend on the emergence or exaltation of tumor markers in peripheral blood:CEA,CA19-9,CA72-4 and so on, but with low sensitivity and poor specificity.The current studies found that CK19 and EpCAM had high expression in breast cancer,gastric cancer,colon cancer,pancreatic cancer,esophgeal cancer and others but no expression in normal hematopoietic tissue and lymph nodes,however,the relationship between the expression of CK19,EpCAM and the diagnosis of gastric cancer and its biological behavior is uncer- tain now.Objective:This study using tissue microarray technology , from the perspective of evidence-based medicine to explore the function of CK19 and EpCAM expression in the secondary prevention of gastric cancer,aimed at finding gastric tumor markers which are sensitive and specific in early diagnosis,so as to provide scientific basis for the secondary prevention and treatment decision- making.Methods:Select 31 cases gastric cancer and 7 cases precancerous lesion including intestinal metaplasia and dysplasia as experimental group from the specimen- tissue bank which had not preoperatively undergone radiotherapy and chemoth- erapy,and select 16 cases normal gastric mucosa as the control group,build experimental tissue chip and use streptavidin peroxidase(SP) immun- ohistoc- hemistry to detect the expression of CK19 and EpCAM in the chips.Then use the diagnostic test evaluation method of evidence-based medicine to evaluate the effect of the two proteins and tissue microarray technology in the diagnosis of gastric cancer.Results:This experiment successfully constructed tissue microarrays containing normal tissue,precancerous lesions and cancer organizations,which were seen with non-shedding and good morphous by the HE staining. The immuno- histochemically stained result is good,positive signals are clearly shown with brown-yellow particles,the background was cleaned and positive position is accurate:CK19 expressed in cytoplasm,EpCAM expressed on the cell membrane.The statistical analysis shows that(1)CK19,EpCAM expressed higher in precancerous lesions and gastric cancer tissues than in normal tissues(P<0.05),(2)CK19 expressed in cancer tissue has no significant correlation with gender,age,histological type,differentiation,tumor location,general type, lymph node metastasis,depth of invasion,TNM staging and so on(P>0.05),while the expres- sion of EpCAM is related to the depth of invasion(P<0.05),TNM staging (P<0.05),lymph node metastasis(P<0.05).Through evidence-based laboratory diagnostic methods evaluating and generally analyzing:EpCAM and EpCAM with CK19 in parallel experiments have the highest diagnostics value,the sensitivity are 65.8% and 86.8% respectively,the specificity are 87.5% and 81.3% respectively, positive likelihood ratio are 5.26 and 4.64 respectively,negtive likelihood ratio are 39.1 and 16.2 respectively,Youden index are 0.533 and 0.681 respectively,consistent rates are 72.2% and 85.1% respectively.The research shows that using tissue microarray technology to detect the expression of CK19 and EpCAM plays a certain role in the secondary prevention of gastric cancer.Conclusion:Currently there are no reports on using CK19 and EpCAM as tissue microarray detection.In this study,successful construction of gastric mucosal tissue microarray ,through comparing the expression of the two proteins CK19 and EpCAM in different gastric mucosal tissues shows that:(1)Both CK19 and EpCAM can be used for the secondary prevention of gastric cancer,in which EpCAM can not only used in the early diagnosis of gastric cancer but also has certain designations to lymph node metastasis,depth of invasion,and TNM staging of gastric cancer,and help judge the patient's diagnosis and progno- sis.This study authenticated the evidence-based laboratory diagnostic value of CK19 and EpCAM in the secondary prevention of gastric cancer.(2)The tissue microarray technology in the study of tumor markers is high-throughput and large sampled test techonlogy with small size,high information content,grouping and designing depending on different needs,time-saving and high-speeding,simple and economic,resulting in better comparability .This results provide the possib- ility of using CK19 and EpCAM in the secondary prevention of gastric cancer and lay the foundation that the tissue microarray technology can select the tumor markers of gastric cancer and et al in the future.
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