WNT4 Gene and Protein Expression in Endometrial Cancer and Its Significance

SIMPLE SUMMARY: The dysregulated impact of WNT4 and estrogens disrupts uterine homeostasis and function, potentially escalating the risk of endometrial cancer. This research sought to assess aberrations in WNT4 gene expression and WNT4 protein immunoreactivity in clinical samples of endometrial cancer, with a focus on tumor characteristics, clinicopathological association, and estrogen dependence. Analysis of a large patient cohort provided additional support for studying WNT4 expression. Results provide a valuable basis for further investigation of the molecular mechanism of estrogen-induced endometrial carcinogenesis. ABSTRACT: Background: The inappropriate action of WNT4 and estrogens affects uterine homeostasis and function, and may lead to endometrial cancer (EC). Objective: The aim was to evaluate the alterations of WNT4 gene expression and WNT4 protein immunoreactivity (Ir) in EC, considering tumor characteristics, the clinicopathological association and estrogen dependence. Methods: WNT4 mRNA levels were compared between benign (control) endometrium (n = 8) and endometroid EC (EEC) and non-endometroid EC (non-EEC) samples (n = 28) using the real-time PCR technique. The WNT4-Ir and ERα-Ir were evaluated by immunohistochemistry (IHC). WNT4 mRNA gene and WNT4-Ir were correlated with clinicopathological and blood morphological parameters. Overall survival (OS) was assessed. The bioanalysis was utilized to study WNT4 expression in large patient cohort (n = 549). Results: WNT4 gene expression was decreased in EC samples (specifically in EEC but not in non-EEC) compared to the control. The WNT4 gene expression was also decreased in EC samples categorized by the tumor characteristics. There was no statistical difference in WNT4-Ir or ERα-Ir between the control and EC. There was no correlation between OS and WNT4 gene expression and WNT4-Ir. Bioanalysis showed that WNT4 and ESR1 gene expression alterations tended to be mutually exclusive. An alteration in WNT4 expression was found in different histological tumor types in a large group of EC patients. Conclusions: There is a great need to evaluate the molecular background of EC. Our study suggests that the WNT4 gene has the potential to be a marker of functional estrogen signaling in EEC.