论文部分内容阅读
Objective:1.To evaluate E-cadherin expression and its clinical significance in pancreatic adenocarcinoma; 2. To further clarify if deregulation of the E-cadherin/β-catenin complex might be the cause for cytoplasmic accumulation of β-catenin. Methods:We investigated the expression pattern of E-cadherin and β-catenin on serial sections from 41 pancreatic cancers. Precipitation and Western blot analysis were performed in 12 tumors with anti-E-cadherin antibody. Results:Reduced or entirely negative expression was found in 65.9%(27 of 41) of the tumors studied; 24 of 41 tumors exhibited increased cytoplasmic immunoreactivity. Interestingly, we found a clear inverse correlation between membranous and cytoplasmic expression of E-cadherin in 43 tumors(P＜0.0005).The prognosis was poor with reduced tumor E-cadherin expression (P＜0.05) but not with other clinicopathological parameters (age, sex, tumor grading and TNM stage); Analysis of serial sections stained with anti-β-catenin antibody revealed a marked correlation between aberrant expression of E-cadherin and ectopic accumulation of β-catenin(P＜0.01).Immunoprecipitation of lysates from pancreatic adenocarcinomas and normal pancreas revealed a clear reduced coprecipitation activity of E-cadherin and β-catenin in the carcinoma samples.Conclusions:The finding, that the loss of membranous E-cadherin correlates significantly with cytoplasmic β-catenin expression, which is a factor for poor prognosis, makes a relationship between E-cadherin dysfunction, deregulated β-catenin and activated Tcf transcription possible.