PROX1 and β-catenin are prognostic markers in pancreatic ductal adenocarcinoma

Background: The Wnt/beta-catenin pathway has a key role in regulating cellular processes and its aberrant signaling can lead to cancer development. The role of beta-catenin expression in pancreatic ductal adenocarcinoma is somewhat controversial. Transcription factor PROX1 is a target of Wnt/beta-catenin signaling and it is involved in carcinogenesis through alterations in its expression. The actions can be either oncogenic or tumor suppressive depending on the tissue. The aim of this study was to investigate PROX1 and beta-catenin expression in pancreatic ductal adenocarcinoma (PDAC). Methods: Expression of PROX1 and beta-catenin were evaluated in 156 patients by immunohistochemistry of tissue microarrays. Associations between tumor marker expression and clinicopathological parameters were assessed by the Fischer's exact-test or the linear-by-linear association test. The Kaplan-Meier method and log-rank test were used for survival analysis. Uni- and multivariate survival analyses were carried out by the Cox regression proportional hazard model. Results: High PROX1 expression was seen in 74 (48 %) tumors, and high beta-catenin expression in 100 (65 %). High beta-catenin expression was associated with lower tumor grade (p = 0.025). High PROX1 and beta-catenin expression associated significantly with lower risk of death from PDAC in multivariate analysis (HR = 0.63; 95 % CI 0.42-0.95, p = 0.026; and HR = 0.54; 95 % CI 0.35-0.82, p = 0.004; respectively). The combined high expression of PROX1 and beta-catenin also predicted lower risk of death from PDAC (HR = 0.46; 95 % CI 0.28-0.76, p = 0.002). Conclusion: In conclusion, high PROX1 and beta-catenin expression were independent factors for better prognosis in pancreatic ductal adenocarcinoma.