Histological Grade and Tumor Stage Are Correlated with Expression of Receptor Activator of Nuclear Factor Kappa b (Rank) in Epithelial Ovarian Cancers.

Andrea Martínez-Massa,Octavio Burgués,Antonio Marín-Montes,Miguel Á Tejada,Ana I Santos-Llamas,Víctor Rodríguez-García,Raul Gomez,Antonio Cano,Juan J Tarín

doi:10.3390/ijms23031742

Abstract

The receptor activator of nuclear factor kappa B (RANK) is becoming recognized as a master regulator of tumorigenesis, yet its role in gynecological cancers remains mostly unexplored. We investigated whether there is a gradation of RANK protein and mRNA expression in epithelial ovarian cancer (EOC) according to malignancy and tumor staging. Immunohistochemical expression of RANK was examined in a cohort of 135 (benign n = 29, borderline n= 23 and malignant n = 83) EOCs. Wild type and truncated RANK mRNA isoform quantification was performed in a cohort of 168 (benign n = 26, borderline n = 13 and malignant n = 129) EOCs. RANK protein and mRNA values were increased in malignant vs. benign or borderline conditions across serous, mucinous and endometrioid cancer subtypes. Additionally, a trend of increased RANK values with staging was observed for the mucinous and serous histotype. Thus, increased expression of RANK appears associated with the evolution of disease to the onset of malignancy in EOC. Moreover, in some EOC histotypes, RANK expression is additionally associated with clinicopathological markers of tumor aggressiveness, suggesting a role in further progression of tumor activity.

Highlights

Research Unit on Women’s Health-Institute of Health Research, INCLIVA, 46010 Valencia, Spain; Department of Pathology, University of Valencia, 46010 Valencia, Spain
Staining of normal ovarian sections contained in the tissue microarray (TMA) revealed that receptor activator of nuclear factor kappa B (RANK) was mostly located in the vessel and scarcely in stromal cells (Supplementary Figure S2)
Our study shows that RANK expression is higher in malignant epithelial ovarian cancer (EOC) than in benign or borderline tumors, a pattern consistently reproduced in a separate analysis of the three histological subtypes

Summary

Introduction

We investigated whether there is a gradation of RANK protein and mRNA expression in epithelial ovarian cancer (EOC) according to malignancy and tumor staging. EOCs. Wild type and truncated RANK mRNA isoform quantification was performed in a cohort of 168 (benign n = 26, borderline n = 13 and malignant n = 129) EOCs. RANK protein and mRNA values were increased in malignant vs benign or borderline conditions across serous, mucinous and endometrioid cancer subtypes. A trend of increased RANK values with staging was observed for the mucinous and serous histotype. Increased expression of RANK appears associated with the evolution of disease to the onset of malignancy in EOC. In some EOC histotypes, RANK expression is associated with clinicopathological markers of tumor aggressiveness, suggesting a role in further progression of tumor activity

Methods

Results

Conclusion