Characterization of the Endometrial MSC Marker Ectonucleoside Triphosphate Diphosphohydrolase-2 (NTPDase2/CD39L1) in Low- and High-Grade Endometrial Carcinomas: Loss of Stromal Expression in the Invasive Phenotypes.

Aitor Rodríguez-Martínez,Carla Trapero,August Vidal,Xavier Matias-Guiu,Inmaculada Gómez De Aranda,Mireia Martín-Satué,Jordi Ponce,Jean Sévigny,Josep Maria Piulats,Maria Eulàlia Fernández-Montolí

doi:10.3390/jpm11050331

Abstract

Ectonucleoside triphosphate diphosphohydrolase-2 (NTPDase2/CD39L1) has been described in human non-pathological endometrium in both epithelial and stromal components without changes along the cycle. It was identified as a stromal marker of basalis. In the present study, we aimed to evaluate NTPDase2 distribution, using immunolabeling and in situ enzyme activity approaches, in endometrial carcinoma (EC) at different tumor grades. NTPDase2 was present in tumor epithelial EC cells, as in the non-pathological endometria, but the expression underwent changes in subcellular distribution and also tended to decrease with the tumor grade. In stroma, NTPDase2 was identified exclusively at the tumor-myometrial junction but this expression was lost in tumors of invasive phenotype. We have also identified in EC samples the presence of the perivascular population of endometrial mesenchymal stem cells (eMSCs) positive for sushi domain containing 2 (SUSD2) and for NTPDase2, already described in non-tumoral endometrium. Our results point to NTPDase2 as a histopathological marker of tumor invasion in EC, with diagnostic relevance especially in cases of EC coexisting with other endometrial disorders, such as adenomyosis, which occasionally hampers the assessment of tumor invasion parameters.

Highlights

The human endometrium, the mucous membrane lining the cavity of the uterus, consists of two layers: the functionalis, adjacent to the uterine cavity, which contains the surface epithelium, the glandular epithelium, and a substantial amount of vascularized stroma; and the basalis, adjacent to the myometrium, made up of the basal portions of the glands, a dense stroma, and blood vessels
We have previously demonstrated the expression of the so-called CD39-CD73 axis in endometrial carcinoma (EC), with high ATPase activity in part attributable to NTPDase1, highly expressed in the tumor stroma [26]
We evaluated NTPDase2 expression at the stroma of the endometrial–myometrial junction both in non-invasive and desmoplastic invasive ECs, to determine whether this expression is related to the myofibroblast-like phenotype acquired by some stromal cells in EC

Summary

Introduction

The human endometrium, the mucous membrane lining the cavity of the uterus, consists of two layers: the functionalis, adjacent to the uterine cavity, which contains the surface epithelium, the glandular epithelium, and a substantial amount of vascularized stroma; and the basalis, adjacent to the myometrium, made up of the basal portions of the glands, a dense stroma, and blood vessels. The endometrium is a dynamic tissue with recurring cycles of regeneration to restore the functional layer, shed during menses. This regenerative capacity requires the presence of adult stem or progenitor cells. Despite the robust studies conducted in the field, nicely reviewed by de Miguel-Gómez et al [4], more studies are required to deepen our knowledge of the regenerative capacity of the basalis. This highlights the need for describing endometrial basal stromal markers to provide tools for further study

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