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The Expression Of The E-cadherin And Vimentin In Squamous Carcinoma Of The Cervix And Its Correlation With EMT

Posted on:2014-11-05Degree:MasterType:Thesis
Country:ChinaCandidate:Z ShenFull Text:PDF
GTID:2254330425969780Subject:Obstetrics and gynecology
Abstract/Summary:PDF Full Text Request
[Background] Cervical cancer is the third common malignancy in women worldwide,and in developing countries is a common cancer after breast cancer, is the mostcommon malignant tumors of the female genital tract. In recent years, with thewidespread launch of the cervical cancer screening program, cervical cancer andprecancerous lesions of early diagnosis and treatment has increased. However,invasion and metastasis is still the leading cause of death of patients with cervicalcancer,the study of cervical cancer invasion and metastasis mechanism particularlyare important for early judgment invasion and metastasis in cervical cancer treatmentand prognosis.In most solid tumors, the central tumor cells showed epithelial phenotype, andaround the tumor cells often showed stromal cell phenotype, these cells which havephenotype of mesenchymal cells often have strongly migratory ability, and invadesurrounding normal tissue and the occurrence of distant metastases. This phenomenonis epithelial mesenchymal transition.Currently, the main indicator of epithelial-mesenchymal transition occurred weredecline expression of E-Cadherin and Vimentin expression increased. It were showedthat tumor cells of epithelial origin of the adhesion molecules abnormal structure andfunction resulted that cell-cell adhesion becomes loose, intracellular cytoskeletalproteins changed and lead to the reduced ability of the adhesion between tumor cells,migration increased, and make tumor cells more easily away from the originallocation, transferred to the new organ or tissue in the distance, eventually leading tothe death of cancer patients.E-cadherin is location in the epithelium of humans and animals, and play animportant role in maintaining the integrity and structure of the normal epithelial cells. Abnormal expression of E-cadherin reduced ability of cell adhesion, and causedinvasion and distant metastasis of tumor cells. E-cadherin can affect tumor invasionand metastasis via multiple channels. E-cadherin can inhibit protein degradation insurrounding matrix and basement membrane of tumor cells, and prevent tumor cellbreak through matrix and basement membrane. E-cadherin could regulate theproliferation of tumor cells through epidermal growth factor receptor activatingphosphatidy linositol3-Kinase-AKt. It was confirmed that the down-regulation ofE-cadherin can induce the EMT occurrence in breast cancer, ovarian cancer,nasopharyngeal cancer and other tumor, and is closely related to tumor differentiation,invasion and metastasis.Vimentin, which belongs to cell intermediate filament protein family andconstitutes the cytoskeleton important ingredient, plays a important role inmaintaining morphology of cell and organelle, joining mitosis and differentiation,wound healing, signal transduction, et al. The study found that Vimentin can inhibitapoptosis and up-regulation of Vimentin is closely related to tumor migration,invasion and metastasis in a variety of epithelial tumors. This study by the observationof E-cadherin and Vimentin expression in cervical cancer, and explore its role incervical and whether EMT is working in cervical cancer progression, and seekingcervical cancer diagnosis, assessment of prognosis and new policy of treatmentprovides experimental evidence.[Objective] Through detecting the expression of E-cadherin and Vimentin in HaCaT,C33A, SiHa, CaSki, normal cervical epithelium, CIN and cervical carcinoma and itsrelated to EMT, we explore its role in the progression of cervical cancer.[Methods] Detected the expression of E-cadherin and Vimentin in HaCaT, C33A,SiHa, CaSki,12samples of normal cervical epithelium,34cases of CIN tissues and42cases of cervical squamous cell carcinoma by immunohistochemistry, and analysedthe correlation between EMT with E-cadherin and Vimentin. [Results]1) HaCaT cell showed high expression of E-cadherin and negative expression ofVimentin. The cells including C33A, SiHa and CaSki exhibited high expressionof Vimentin, but E-cadherin was barely observed in these cells.2) The expression of E-cadherin was100%in normal cervical epithelial and thehigh expression of E-cadherin was76.29%in CINI tissues. While the expressionof Vimentin was negative in normal cervical epithelial, and the expression ofVimentin was23.08%in CINI tissues. Among the21CINII or III samples,9cases (42.86%) showed high expression of E-cadherin,7cases (33.33%) withlow expression of E-cadherin,47.62%of these samples were shown lowexpression of Vimentin. Among the42SCC samples,9cases (21.43%) SCCspecimens showed high E-cadherin expression,25cases (59.52%) with lowexpression of E-cadherin. In addition,16.67%(7/42) and71.43%(30/42) of SCCsamples exhibited high and low expression of Vimentin, respectively.3) The high expression of E-cadherin was observed in80%(4/5) of cervical cancertissue of well differentiation,12.50%(2/16) from patients which were moderatedifferentiation and28.57%(6/21) from patients which were poor differentiation.Low expression of E-cadherin was detected in20%(1/5) of cervical cancer tissueof well differentiation,75.50%(12/16) from patients which were moderatedifferentiation and57.14%(12/21) from patients which were poor differentiation.Thus, there was a significant decrease in E-cadherin in cancers from patients whodeveloped poor differentiation compared with cancers form patients withmoderate or well differentiation (P <0.05for both). In addition, among cancers,the expression of E-cadherin in well differentiation was higher than theexpression in moderate differentiation (P<0.05). In5cancers of welldifferentiation,3cases was negative expression of Vimentin and2cases was lowexpression. Low expression of Vimentin was observed in68.75%of moderatedifferentiation cancers and80.95%of poor differentiation cancers; The absenceof expression of Vimentin was observed in12.50%(2/16) of moderatedifferentiation cancers and high Vimentin expression was observed in19.05% (4/21). Thus, there were significant differences between the expression ofVimentin and histologic grade (P<0.05).4) Down-regulation of E-Cadherin and up-regulation of Vimentin were closelyrelated to histological grade and lymph node metastasis of cervical cancer (P<0.05).5) The expression of E-cadherin was inversely associated with Vimnetin expressionin SCC (P<0.05).[Conclusion] Reduced expression of E-cadherin and increased expression ofVimentin were closely related to histologic differentiation and metastasis, and wereinvolved in EMT process. Besides EMT play an important role in the process ofmetastasis and progression of cervical squamous cell carcinoma. The combination of adecrease of E-cadherin and an increase in vimentin might be a valuable indictor incervical squamous cell cancer.
Keywords/Search Tags:Cervical cancer, E-cadherin, Vimentin, EMT
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