Epithelial-Mesenchymal Transitional Markers in Endometrial Carcinoma: A Review of Clinicopathological Correlation

Endometrial carcinoma is the most frequently diagnosed gynaecological malignancy in developed countries, and its global incidence continues to increase. Myometrial invasion and lymphovascular spread, driven by epithelial-mesenchymal transition (EMT), are among the most important determinants of clinical outcome. EMT is a dynamic biological process in which epithelial cells develop migratory and invasive mesenchymal characteristics under the influence of transcription factors including SNAIL (SNAI1), SLUG (SNAI2), TWIST, and ZEB2. The aims of this review are to review the current evidence on the immunohistochemical (IHC) expression of the four important EMT transcription factors (SLUG, TWIST, SNAIL, and ZEB2) in endometrial carcinoma and to focus on their clinicopathological correlations, prognostic implications, signalling mechanisms, and potential as therapeutic targets. We conducted a narrative review of the published literature in English using the PubMed, Scopus, and Google Scholar databases. We retrieved and reviewed articles on IHC or molecular expression of SLUG, TWIST, SNAIL, and ZEB2 in endometrial carcinoma. SLUG overexpression independently predicted the advanced International Federation of Gynecology and Obstetrics (FIGO) stage, deep myometrial invasion, lymphovascular space invasion (LVSI), and poorer five-year survival. TWIST expression showed a significant association with the depth of myometrial invasion and loss of E-cadherin expression and was also found to be an independent prognostic factor in multivariate analysis. SNAIL correlates with histological grade, peritoneal cytology positivity, and non-endometrioid histology. High levels of ZEB2 are related to adnexal involvement and higher FIGO stage. Together, these four markers represent a prognostically relevant panel of markers reflecting the invasive phenotype of endometrial carcinoma, which might be targets for novel therapeutic intervention.