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The Study Of Clinical Significance Of Epithelial-mesenchymal Transition Associated Markers In Gastric Cancer

Posted on:2009-01-16Degree:MasterType:Thesis
Country:ChinaCandidate:W J YangFull Text:PDF
GTID:2144360245453000Subject:Oncology
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Gastric cancer is one of the most frequent malignant neoplasms in the gastrointestinal tract,with higher incidence and mortality rate.The mortality rate is the highest in China,and the second in the world. Recent studies have demonstrated that epithelial-mesenchymal transition(EMT)plays an importmant role in invasion and metastasis of all kind of epithelial malignancies.Epithelial-mesenchymal transition was defined as a process characterized by loss of polarization and cell-cell adhesion and gain of fibroblastoid phenotypes and cell motility. During epithelial-mesenchymal transition,the epithelial markers such as E-cadherin andβ-catenin expression are down-regulation,while mesenchymal markers such as N-cadherin is up-regulation.So we immunohistochemically examined the expression of EMT associated markers:E-cadherin,β-catenin and N-cadherin,to investigate the effect of EMT in invasion and metastasis of gastric cancer.Materials and methodsAmong the 82 patients with gastric cancer who underwent gastrectomy at Hangzhou Second Hospital,from January in 2002 to January in 2008.All specimens were fixed with 10%formalin solution, embedded in paraffin,and cut into 4μm-thick sections.The diagnosis of gastric cancer was made by two pathologists.The 82 patients,in this study include 63 male and 19 female.The patients aged 33-83 years (mean 60.3).Mass diameter was from 0.4cm to 18.0cm(mean 4.2cm).A total of 82 samples were performed with Envision immunohistochemistry for detection of E-cadherin,β-catenin and N-cadherin.Evaluation of immunostaining results as follows: E-cadherin expression in the tumors was graded according to the proportion of positive cells.E-cadherin expression was considered to be high E-cadherin group if>90%of cancer cells exhibited a cellular membrance staining pattern similar to that in normal epithelial cells,and sections with 10-90%of cancer stained were defined as low pattern, sections with<10%of cancer stained were defined as loss pattern.β-catenin expression was defined as four patterns:highβ-catenin group if>90%of cancer cells exhibited a cellular membrance staining pattern similar to that in normal epithelial cells,and sections with 10-90%of cancer stained were defined as low pattern,sections with<10%of cancer stained were defined as loss pattern:Heterotopic expression ofβ-catenin was defined as cytoplasmic or nuclei staining of more than 10%.Based on the expression pattern of the E-cadherin andβ-catenin,the specimens were then divided into five groups:high expression group in which E-cadherin andβ-catenin were both highly expressed;low expression in which E-cadherin was lowerly expressed andβ-catenin was lowerly expressed or absent;non-expression group in which E-cadherin andβ-catenin were not expressed;heterotopic expression group in whichβ-catenin was stained in cytoplasmic or nuclei,while E-cadherin highly to absent expressed;separate expression group in which E-cadherin highly expressed whileβ-catenin was lowerly expressed or absent.E-cadherin andβ-catenin low expression, non-expression,heterotopic expression and separate expression were defined as abnormal expression.The samples were classified into two groups based on the intensity of staining of N-cadherin in cancer cells, that is>20%of cancer cells were stained as positive expression,≤20%cancer cells were stained as the negative.Statistical analysis was performed using SPSS13.0 softwares,relationships between the clinicopathologic characteristics and E-cadherin,β-catenin,N-cadherin were examined with the x~2 test,P value<0.05 were considered as statistically significance.RESULTS:High expression of E-cadherin andβ-catenin was found in 20.7%(17/82),abnormal expression was found in 79.3%(55/82) of gastric cancer.Abnormal expression of E-cadherin andβ-catenin correlated with depth of invasion,poor differentiation,TNM stage and Borrmann types.Abnormal expression of E-cadherin andβ-catenin was not correlated with the patient's age,sex,location,tumor size,lymph node metastasis and distant metastasis.N-cadherin expression was correlated with Borrmann types,depth of invasion,poor differentiation, lymph node metastasis and TNM stage.Expression of N-cadherin did not correlated with the patient's age,sex,location,tumor size and distant metastasis. Conclusion1,In gastric cancer,lower or abnormal expression of E-cadherin andβ-catenin were correlated with Borrmann types,depth of invasion,poor differentiation,TNM stage,which indicated that they be correlated with invasion and metastasis of gastric cancer.2,In gastric cancer,higher expression of N-cadherin was correlated with Borrmann types,depth of invasion,poor differentiation,lymph node metastasis and TNM stage,which indicated that up-regulation of N-cadherin play an important role in invasion and metastasis of gastric cancer.3,In gastric cancer,abnormal expressions of E-cadherin andβ-catenin were correlated with up-regulation of N-cadherin, which indicated that in gastric cancer evolvement there should be exist epithelial-mesenchymal transition,which be involved in invasion and metastasis of gastric cancer.
Keywords/Search Tags:gastric cancer, E-cadherin, β-catenin, N-cadherin, Immunohistochemistry, epithelial-mesenchymal transition(EMT)
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