Abstract
BackgroundThe Wnt/β-catenin pathway has a key role in regulating cellular processes and its aberrant signaling can lead to cancer development. The role of β-catenin expression in pancreatic ductal adenocarcinoma is somewhat controversial. Transcription factor PROX1 is a target of Wnt/β-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 β-catenin expression in pancreatic ductal adenocarcinoma (PDAC).MethodsExpression of PROX1 and β-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.ResultsHigh PROX1 expression was seen in 74 (48 %) tumors, and high β-catenin expression in 100 (65 %). High β-catenin expression was associated with lower tumor grade (p = 0.025). High PROX1 and β-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 β-catenin also predicted lower risk of death from PDAC (HR = 0.46; 95 % CI 0.28–0.76, p = 0.002).ConclusionIn conclusion, high PROX1 and β-catenin expression were independent factors for better prognosis in pancreatic ductal adenocarcinoma.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2497-5) contains supplementary material, which is available to authorized users.
Highlights
The Wnt/β-catenin pathway has a key role in regulating cellular processes and its aberrant signaling can lead to cancer development
In the whole tumor specimens, there was no nuclear staining in the metastases; only negative or weak cytoplasmic staining was present (Fig. 1)
We evaluated the staining of prospero homeobox protein 1 (PROX1) in the cytoplasm, whereas in the previous studies of colorectal cancer (CRC), hepatocellular carcinoma (HCC), and gliomas, only the staining in tumor cell nuclei were evaluated [24, 28, 33]
Summary
The Wnt/β-catenin pathway has a key role in regulating cellular processes and its aberrant signaling can lead to cancer development. The Wnt/β-catenin signaling pathway has a role in regulating cellular processes including organ development and differentiation, and tissue homeostasis in adults [1]. In pancreatic ductal adenocarcinoma (PDAC), the role of the Wnt/β-catenin signaling pathway is controversial because of the variable and sometimes paradoxical effects. Genetic alterations of the Wnt signaling pathway are involved in PDAC tumors [6], mutations of APC or CTNNB1 are less common [7]. Heiser et al showed in mice that by introducing a β-catenin stabilizing mutation in CTNNB1 leads to pancreatic hypoplasia at an early phase of the developing pancreas. If this mutation is introduced in later phase in the developing pancreas, it results in enlargement of the exocrine pancreas without tumor formation [8]
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