Expression Of Epithelial Cadherin, β-Catenin And P53 Protein In Human Esophageal Squamous Cell Carcinoma: Relationships With Tumor Progression And Prognosis

Background Esophageal carcinoma was generally considered one of the most extremely aggressive carcinomas with dismal prognosis identified thus far, Previous studies have shown status of intercellular adherens junction played a pivotal role in tumor growth, invasion, metastasis and prognosis. Different expression of adhesion molecules could reflect biologic characteristics of tumor and their detection were conducive to predict and evaluate risk of relapse and metastasis of postoperative esophageal carcinoma, thus having realistic significance to guide individuated treatment. The cadherins that exist many kinds of cell belong to a family of transmembrane glycoproteins responsible for homophilic interaction of calcium-dependent cell-cell adhesion. Among them epithelial cadherin(E-cd) , a member of classic cadherins, and P -catenin( 3 -cat),a multifunctional cytoplasmic protein which linkes E-cadherin and a -catenin to microfilament cytoskeleton constituted E-cadherin-catenins complex. In addition, P -catenin plays an important role in Wingless/Wnt signaling transudation pathway. Reduced and absent expression of them were frequently observed in tumor cells and could destroy structure of complex and disturb intercellular adherens junction and facilitate tumor dedifferentiation, invasion and metastasis, so evaluation of which had some prognostic significance. However, only few studies were available about esophageal squamous cell carcinoma(ESCC). Nowadays it was accepted that mutation of p53 gene as a hallmark or signal might be involved in early stages of carcinogenesis, but relation between aberration of p53 protein and biologic behavior and prognosis in ESCC remain controversial . Moreover, In some kinds of tumor p53 status was associated with E-cd-mediated adherens junction system and affected expression of E-cd and 3 -cat, stymied the formation of E-cadherin-catenins complex, At the same time 3 -cat inhibited degradation of p53 protein and p53-dependent apoptosis process and biologic behavior of tumors. But few studies were carried out in ESCC. To elucidate whether the expression of E-cd , P -cat and p53 correlate with clinicopathological variables, by analyzing mutual connections and effect on development of tumors and discussing their roles in development and prognostic evaluation in ESCC. Furthermore, may provide some considerable suggestions for clinical treatments. Methods Expression of E-cd , P -cat and p53 wereretrospectively determined by S-P immunohistochemical technique in consecutive patients with ESCC,and their correlation with characteristics of clinical materials were evaluated and performed to compare by multivariate analysis. Results (1) Reduced expression of E-cd was found in 70 (66.03%) of 106 patients and level of protein had inverse correlation with histologic grade, tumor size, clinical stage, lymph node status and venous invasion. Whereas reduced expression of P -cat in 74 cases (69.8%)correlated only with histologic grade. (2) Different E-cd/ P -cat status were associated with histologic grade, tumor size and clinical stage; Analyzed by tumor stage, the reduction rate of expression in tumors with grade III, stage III or IV, and tumors more than 5.0cm in length were higher than that of grade I or II, stage I or II, and tumors less than 5.0cm in length; In NO group, the reduction of E-cd/ 3 -cat expression occurred more significantly often in tumors whose invasion was beyond muscularis propria than in tumors confined to mucosa and submucosa (T1,T2 vsT3,T4 /M).041). (3) The intensity of E-cd positively correlated with that of P -cat (.P=0.005). (4) Cytoplasm expression in thirty-six cases(33.96%) for E-cd and in 39 cases(36.79%) for P -cat, of which the cytoplasm level of E-cd protein in altered membranous expression was lower than that of normal ones , had no significance with clinicopathological parameters, and the cytoplasm level of 3 -cat protein was higher in category T3,4 than in category Tl,2 according to invasion depthCP=0.022).(5) Forty-nine out of 106 cases (46.23%) for p53...