The Expressions Of Claudin-3 And Claudin-4 In Colorectal Adenoma And Colorectal Carcinoma

Objective: With the improvement of people’s living level and changes in diet,the morbidity and mortality of colon cancer has been growing year after year in recent years,which seriously affect people’s health and shorten expective life. At present, it is considered that the colorectal cancer occour by three main pathway: the adenoma- carcinoma sequence, ulcerative colitis-colorectal cancer pathway and Juvenile Polyposis Syndrome pathway. The adenoma- carcinoma sequence account for vast majority. APC mutations cause normal mucosal epithelial cell hyperplasia, DNA methylation abnormalities promote adenoma formation, then due to Ras mutation,deletion of DCC and P53 mutation form adenocarcinoma. In addition, microsatellite instability is also the pathogenesis factor of hereditary non-polyposis colorectal cancer.Whatever the reason, formation of cancer stem cell is undoubtedly the key factor. Cancer stem cells origining from the epithelial may undergo the epithelial-mesenchymal transition, leading to cancer stem cell with mesenchymal characteristics appearing, many studies showed that claudin is the key factor of forming epithelial-mesenchyme-cancer stem cell. Claudins are the important integral proteins of the tight junction,which are the blocking proteins. Tight junctions are the most important cell-cell junction in the gastrointestinal mucosa epithelial cell,which locate in the apical of the cell, and operating fence and barrier function.Tight junction contains claudins, occludins, ZOs, junctional adhesion molecules(JAM),and so on. Changes in the structure and function of claudins can lead to many changes in tight junction. Alterations in TJ permeability may allow diffusion of nutrients,which can promoting growth of tumor, the damage of cell and tight junction result in loss of contact inhibition, then the integration of adjacent cell make cancer cells increase multiplely, spread to distance along the lymph and blood. Claudin-3 and claudin-4 both originate from 7q11.23, a number of studies suggest that in colon carcinoma, the expression of claudin-3 and claudin-4 both increase, but there are some opposite conclusion, the expression of claudin-4 was decreased in metastatic colorectal cancer.This experiment is designed to detect the expression of claudin-3 and claudin-4 in normal colorectal mucosa, different histological types of colorectal adenoma and colorectal cancer, to explore their functions to predict the malignant transformation of colorectal adenomas, and looking forward to providing some evidence for claudins as the disease prognosis factors.Method:60 cases of colorectal carcinoma were obtained from January 2012 to June 2013, from the general surgery department of No.252 hospital of Chinese People’s Liberation Army,and 40 normal colorectal mucosa tissues were matched as control(which is also called normal tissue adjacent to carcinoma, taken from the surgical removal residual,distance carcinoma tissue more than 5cm).All of patients had no preoperative chemotherapy, and targeted therapy. 90 colorectal adenomas including 30 tubular adenoma, 30 mixed pattern of adenoma, 30 villous adenoma were collected from Digestive Endoscopy Center of No.252 of P.L.A.All specimens were confirmed for histopathological examination and screening by senior physician.Measurements: HE dyeing observation of colorectal adenomas and colorectal cancer and normal colorectal mucosa of the microscopic morphology were used to differentiate the pathological type of colorectal adenomas and tissue differentiation degree. Using immunohistochemistry technique to detect claudin-3, claudin-4 localization in cells and expression.Data statistics and analysis:The results were analyzed by chi-square criterion with SPSS17.0.All reported P value were 2 sided and the test was considered to be statistically significant when P<0.05.Results:1 The positive expression rates of claudin-3 protein in normal colorectal mucosa, colorectal adenoma and colorectal carcinoma tissues were 12.5%,41.1%,73.3%, respectively, with significant differences among them(P<0.05). The positive expression rates of claudin-3 in tubular adenoma, mixed pattern of adenoma, villous adenoma were 23.3%, 43.33%, 56.67%, respectively,also with significant differences among them(P<0.05).2 Claudin-4 mainly distribute in normal intestinal cavity epithelium cell membranes and cytoplasm, in adenoma there is more in the cytoplasm, the same to the colorectal cancer.It was highest expression in adenoma, and in colorectal cancer the expression decreased, there were significant differences(P<0.05),among them the position expression rate were 55%,67.8%,43.3%, respectively.In the three different adenomas, the villous adenoma expressed superlatively. The positive expression rate among tubular adenoma, mixed pattern of adenoma, villous adenoma were 46.67%、70.0%、86.67%.Conclusions:1 Claudin-3 is closely to the occurrence of colorectal cancer and the malignancy of colorectal adenoma.The rate of villous adenoma malignancy is higher than the tubular adenoma and mixed pattern of adenoma, it is more closely related to the occurrence of colorectal cancer. Claudin-3 can evaluate the progression of colorectal adenoma and the development of colorectal carcinoma. It may be the molecular biological indicators for predicting malignant transformation from colorectal adenoma.2 Claudin-4 exist in the normal intestinal epithelium,it expressed highly in the adenoma, expressed highest in villous adenoma, but expressed lowly in the colorectal cancer. Its role need to be further investigated.