Abstract
Endometrial cancer (EC) is the sixth deadliest cancer in women. The depth of myometrial invasion is one of the most important prognostic factors, being directly associated with tumor recurrence and mortality. In this study, ALCAM, a previously described marker of EC recurrence, was studied by immunohistochemistry at the superficial and the invasive tumor areas from 116 EC patients with different degree of myometrial invasion and related to a set of relevant epithelial and mesenchymal markers. ALCAM expression presented a heterogeneous functionality depending on its localization, it correlated with epithelial markers (E-cadherin/β-catenin) at the superficial area, and with mesenchymal markers at the invasive front (COX-2, SNAIL, ETV5, and MMP-9). At the invasive front, ALCAM-negativity was an independent marker of myometrial invasion. This negativity, together with an increase of soluble ALCAM in uterine aspirates from patients with an invasive EC, and its positive correlation with MMP-9 levels, suggested that ALCAM shedding by MMP-9 occurs at the invasive front. In vivo and in vitro models of invasive EC were generated by ETV5-overexpression. In those, we demonstrated that ALCAM shedding was related to a more invasive pattern and that full-ALCAM recovery reverted most of the ETV5-cells mesenchymal abilities, partially through a p-ERK dependent-manner.
Highlights
Endometrial cancer (EC) is the most common gynecologic cancer and the sixth most deathly cancer in women from western countries [1]
We studied the immunohistochemical expression of Activated-leukocyte cell adhesion molecule (ALCAM) extracellular domain and a representative set of epithelial (E-cadherin/β-catenin major adhesion complex) and mesenchymal molecules involved in endometrial cancer (EEC) dissemination (ETV5, COX-2, SNAIL, SLUG, MMP-2 and -9), in both the superficial and the invasive areas of the tumor
As our previous results indicated a different behavior of ALCAM regarding tumor differentiation, analyses were performed in the entire population, and in the well-differentiated (GI) and poorlydifferentiated (GII-III) subcohorts [32]
Summary
Endometrial cancer (EC) is the most common gynecologic cancer and the sixth most deathly cancer in women from western countries [1]. Myometrial invasion is one of the most important prognostic factors of EC and represents an increase in the rate of recurrence and a decrease in the 5-year survival [2]. The first step of myometrial invasion is characterized by the dissociation of tumor cells from the epithelial layer of the endometrial glands, and their subsequent infiltration through the basement membrane into the adjacent layer, the myometrium [3]. It is known that in invading tumors this process takes place at the invasive front [4,5,6]. EMT is a dynamic process controlled by external signals coming from the tumor cells microenvironment, that involves cellular loss of polarity, loosen cell-cell contacts, reorganization of cytoskeleton and acquisition of plasticity, motility and invasive capabilities. Multiple factors have been described as being responsible for producing EMT in EC, such as ETV5, estrogen and progesterone receptors, and TGF-β, among others [3]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
