Epithelial-Mesenchymal Transition Markers beta-catenin, Snail, and E-Cadherin do not Predict Disease Free Survival in Prostate Adenocarcinoma: a Prospective Study

Abstract

Current methods for diagnosis and staging of prostate adenocarcinoma are not sensitive enough to distinguish between patients with indolent disease and those that should receive radical treatment. Epithelial-mesencyhmal transition (EMT) is a well-characterized process involved in tumor invasion and metastasis. The aim of this study is to analyze the expression of beta-catenin, Snail, and E-cadherin in prostate cancer patients with prospective evaluation of their value in predicting disease-free survival (DFS). One-hundred-and-three consecutive prostate carcinoma patients who underwent radical prostatectomy and 35 patients with benign prostate hyperplasia (BPH) were enrolled. Age, initial PSA level, tumor size and clinical stage were documented for adenocarcinoma patients and they were enrolled in active surveillance with serum PSA levels. Recurrence was defined as PSA level of a parts per thousand yen0.2 ng/ml on at least 2 occasions over a 2-month period. Immunohistochemical staining intensity was scored as negative, weakly positive, moderately positive, and strongly positive. For Snail and beta-catenin immunoreaction, the tumors were considered nuclear positive when more than 5 % of the nuclei of tumor cells were positively stained. Patients with prostate cancer had weaker beta-catenin (p < 0.0001), Snail (p = 0.006), and E-cadherin (p = 0.02) staining when compared to BPH patients and the frequency of nuclear positivity for beta-catenin and Snail were higher in adenocarcinoma group (p < 0.0001). Increased expression and nuclear positivity of beta-catenin were associated with advanced stage (p = 0.012 and p = 0.003) and higher tumor volume (p = 0.013 and p = 0.002). Additionally, patients with increased Snail expression had higher Gleason scores and tumor volume at presentation (p = 0.008 and p = 0.004). However, there were no significant DFS differences in adenocarcinoma patients who did and did not have beta-catenin, Snail, and E-cadherin expression as assessed with log-rank test. Expressions of beta-catenin, Snail, and E-cadherin were significantly lower in prostate cancer patients compared to BPH patients and both beta-catenin and Snail had nuclear staining pattern in patients with adenocarcinoma. However, none of these markers predicted DFS in 36-month follow up of our cohort.