WNT4 Gene and Protein Expression in Endometrial Cancer and Its Significance

Jolanta Kiewisz; Tomasz Waśniewski; Jacek Kieżun; Agnieszka Skowrońska; Monika M Kaczmarek; Błażej Szóstak; Anna E Kowalczyk; Zbigniew Kmieć

doi:10.3390/cancers15194780

WNT4 Gene and Protein Expression in Endometrial Cancer and Its Significance

Cancers (Basel). 2023 Sep 28;15(19):4780. doi: 10.3390/cancers15194780.

Authors

Jolanta Kiewisz¹, Tomasz Waśniewski², Jacek Kieżun¹, Agnieszka Skowrońska³, Monika M Kaczmarek⁴, Błażej Szóstak⁵, Anna E Kowalczyk¹, Zbigniew Kmieć^{1

6}

Affiliations

¹ Department of Human Histology and Embryology, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, Poland.
² Department of Gynecology and Obstetrics, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, Poland.
³ Department of Human Physiology, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, Poland.
⁴ Department of Hormonal Action Mechanisms, Institute of Animal Reproduction and Food Research, Polish Academy of Science, 10-748 Olsztyn, Poland.
⁵ Department of Pathomorphology, The Regional Specialist Hospital, 10-561 Olsztyn, Poland.
⁶ Department of Histology, Medical University of Gdansk, 80-211 Gdansk, Poland.

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.

Keywords: IHC; WNT4; endometrial cancer; estrogen; qPCR.

Grants and funding

The research was financed from statutory grant (61.610.001-110) of School of Medicine, Collegium Medicum, University of Warmia and Mazury, Olsztyn, Poland.