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Expression Of EP-CAM, Beta-catenin In The Cacinogenesis Of Cervical Squamous Cell Carcinoma And Its Relationship With HPV Infection

Posted on:2003-12-24Degree:MasterType:Thesis
Country:ChinaCandidate:J Z YangFull Text:PDF
GTID:2144360065950200Subject:Pathology and pathophysiology
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Objective: Cervical carcinoma is one of the most frequently seen malignancies in female with high incidence in the developing countries. Recently, there is an increasing tendency in the incidence among younger women. In the past decades, many studies on different aspects have been carried out on cervical carcinoma, but up to now, the carcinogenesis of cervical carcinoma is still not clear enough.Epithelial cell adhesion molecule (EP-CAM), also called 17-1 A, ESA, EGP40, is a 40KDa epithelial transmembrane glycoprotein, encoded by the GA733-2 gene, to function as a homophilic cell adhesion molecule, in a Ca2+ - independent manner in benign and malignant epithelial cells. Beta - catenin is a kind of cell bone protein. It binds to E-cadherin and mediates the adhesion among the same kinds of cells, highly associated with tumor's invasion and metastasis. On the other hand, Beta-catenin is involved in the Wg/Wnt signaltransductionpathway, composed by APC/ -catenin/Tcf/Lef-1, associated with embryo growth and carcinogenesis of carcinoma.Human papillomaviruses (HPVs) were found to be associated with the incidence of cervical carcinoma. Of the about 100 different types of HPV that have been categorized to date, approximately thirteen were associated with cervical carcinoma. Based on the relationship between subsets of HPVs and female genital cancers, HPVs were categorized into "high - risk' HPVs and 'low - risk' HPVs. Of the 'high - risk' HPVs, HPV-16 is highly associated with cervical squamous cell carcinoma. It has been generally accepted that HPVs play an important role in the carcinogenesis of cervical carcinoma. However only a small proportion of cervical intraepithelial lesions infected with 'high - risk" HPVs will progress to invasive cervical carcinoma, which indicates the involvement of additional factors.The clinical significance of the expression of EP-CAM and beta-catenin in breast cancer and laryngeal cancer has been reported. The putative contribution of them in the carcinogenesis of cervical carcinoma and their relationship with HPV-16 infection was still unclear.To explore the possible roles of EP-CAM and beta-catenin expression in the carcinogenesis of cervicalcarcinoma and elucidate the relationship between their expression and HPV-16 infection, the expressions of EP-CAM and beta-catenin as well as existence of HPV-16 DNA in normal cervical epithelium, CIN and cervical invasive carcinoma were investigated in this study.Methods: EP-CAM, beta-catenin expressions were studied with immunohistochemical stainning in 14 cases of normal cervical epithelium, 32 cases of CIN and 38 cases of cervical invasive squamous cell carcinoma. At the same time, HPV-16 DNA was detected using polymerase chain reaction (PCR) in these cases. The relationship between the expression of EP-CAM and beta-catenin and clinical pathological features as well as HPV-16 infections was also studied.Results: 1. EP-CAM expression: No or very weak expression of EP-CAM was found in 14 cases of normal cervical epithelium, while over-expressions could be found in some CIN and carcinoma cases. The over-expression rates of EP-CAM was 7.14%, 20.00%, 62.50%, 55.26% for CIN1, CIN2,CIN3 and carcinoma groups respectively. The rates of over-expression of EP-CAM in CIN3 and cervical carcinoma groups were all significantly higher than these in normal epithelium and CIN1 groups (P < 0.001). There is no significant difference between CIN3 group and cervical squamouscell carcinoma group in the over-expression rates(P> 0.05). 2. Beta-catenin expression: beta-catenin was localized only on the plasma membrane of the basal and parabasal layer cells in normal cervical squamous epithelium. In some cases of CIN and squamous cell carcinoma cases, aberrant expression (no expression, cytoplasmic or/and nuclear expressions) of beta-catenin was observed. Aberrant expression rates of beta-catenin increased from normal epithelium, CIN to cervical carcinoma. The aberrant expression rate for CIN1, CIN2, CIN3 and carcinoma gr...
Keywords/Search Tags:cervical squamous cell carcinoma, cervical intraepithelial neoplasm, human papillomavirus, EP-CAM, beta-catenin, PCR, Immunohistochemical stainina.
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