Phenotypic Profile of Microsatellite Stable with Epithelial to Mesenchymal Transition Subtype in Gastric Adenocarcinoma

Abstract

The microsatellite stable with epithelial to mesenchymal transition (MSS/EMT) subtype includes some of the most aggressive gastric tumors with the worst prognosis. The purpose of this study is to characterize the MSS/EMT subtype by investigating potential associations with clinicopathologic features and specific elements of the tumor microenvironment: tumor-infiltrating lymphocytes and tumor budding. From a retrospectively collected bi-centric cohort, we first selected microsatellite stable samples and then assessed the immunohistochemical expression of E-cadherin, β-catenin, and zinc finger E-box binding homeobox 1 to identify the epithelial to mesenchymal transition. Our findings revealed that the MSS/EMT subtype represented 43% of our series, which was a high prevalence compared to previous studies. This subtype included patients who were significantly younger than non-MSS/EMT patients (p = .017). It was associated with diffuse and mixed-type histology (p = .047) and with nonconventional carcinomas (p = .023). The MSS/EMT did not correlate with the advanced stage. Regarding the tumor microenvironment elements, the MSS/EMT subtype was associated with low density of tumor-infiltrating lymphocytes (p < 10⁻³), while no association was found with tumor budding score. In conclusion, the highly prevalent and distinct MSS/EMT gastric cancer subtype features low tumor-infiltrating lymphocyte density, suggesting an immunosuppressive tumor microenvironment and therapy resistance.