Expression Characteristics And Clinical Significance Of Wnt2 And β-catenin In Esophageal Cancers

Backgrounds and Objectives:Esophageal cancer (EC) is one of the commonest malignancies that dangerous to people's health. The carcinogenesis of EC relates to activation of oncogene and inactivation of anti-oncogene. The exact mechanism of EC is still unclear, and the lackage of accurate and effective method for early diagnosis is the main cause to induce the high mortality of EC. At present, the unfavourable prognosis is about 10% of 5-year-survival rate. Therefore, exploration of genetic alterations closely linked with EC formation and dissemination would be of great values in prevention, early detection and prognostic evaluation of this malignancy.Multiple molecular changes have been studied, among which Wnt signaling is one of the key path. The activation of this signaling represented by the up-regulation of Wnt2 andβ-catenin is closely related to carcino-genesis. It has been well documented in gastric, hepatic, colorectal, pancreatic, prosted and mammary cancer that increased expression of Wnt2 andβ-catenin serves as a biological indicator of cell dedifferentiation and patients'poor prognosis.This study aimed to profile expression of Wnt2 andβ-catenin during stepwise esophageal carcinogenesis and to analyze the relationship to the series of pathological factors through the methods of microarray and immunohistochemistry stain.Materials and Methods:EC, precancerous lesions and relative normal esophageal tissues were all selected from the Anshan City Tumour Hospital from 1999-2008. All the exairesis samples were conclusive diagnosed without chemoradiotherapy. By the methods of paraffin embedded tissue array immunohistochemistry, the expression pattern of Wnt2 andβ-catenin in different esophageal tissues were detacted, the correlation between Wnt2 andβ-catenin expression and EC invasiveness and metastasis was analyzed. The data were statistically analyzed by Kruskal-Wallis, Mamm Whitney and Spearmen with SPSS 11.0 software.Results:1. It was found that the stepwise up-regulation rate of Wnt2 andβ-catenin in noncancerous tissues, premalignant tissues and cancer samples was significant in statistical analyses with Kruskal-Wallis test and Mann-Whitney test (p=0.000). There were significant differences of Wnt2 andβ-catenin upregulation both between the EC group and noncancerous mucosa or premalignant lesions and between the ESCC and adencarcinoma group (p=0.015/0.031), excluding between noncancerous and premalignant epitheial (p=0.136/0.452).2. Close correlation of Wnt2 andβ-catenin expression could be observed (p=0.000, r=0.740).3..No significant difference among gender, age group, differentiation level and different tumor size group (p>0.05). 4.Statistical significance could be established between LN negative and positive group, T3,4 and T1,2 group and theⅢ-Ⅳstage andⅠ-Ⅱstage (p<0.005).Conclusion:1. The expression of Wnt2 andβ-catenin gene, which is the presentation of Wnt signaling, is an important molecular event throughout the whole EC carcinogenesis. The expression frequency increased from noncancerous tissues to tumor.2. Wnt2 andβ-catenin upregulation is closely related to the invasion and metastases of EC which indicate that Wnt signaling contributes to invasion and progression of EC and is of important value in molecular diagnosis and prognosis prediction.