Immunohistochemical Markers of the Epithelial-to-Mesenchymal Transition (EMT) Are Related to Extensive Lymph Nodal Spread, Peritoneal Dissemination, and Poor Prognosis in the Microsatellite-Stable Diffuse Histotype of Gastric Cancer

Abstract

Background: Although the prognostic value of the epithelial-to-mesenchymal transition (EMT) in gastric cancer has been reported in several studies, the strong association with the diffuse type may represent a confounding factor. Our aim is to investigate potential correlations among EMT status, tumor advancement, and prognosis in diffuse gastric cancer. Methods: Between 1997 and 2012, 84 patients with microsatellite-stable (MSS) diffuse-type tumors underwent surgery. The EMT phenotype was assessed with the E-cadherin, CD44, and zinc finger E-box binding homeobox 1 (ZEB-1) immunohistochemical markers. Results: Forty-five out of 84 cases (54%) were EMT-positive; more advanced nodal status (p = 0.010), pTNM stage (p = 0.032), and vascular invasion (p = 0.037) were observed in this group. The median numbers of positive nodes (13 vs. 5) and involved nodal stations (4 vs. 2) were higher in the EMT-positive group. The cancer-related survival time was 26 months in EMT-positive cases vs. 51 in negative cases, with five-year survival rates of 17% vs. 51%, respectively (p = 0.001). The EMT status had an impact on the prognosis of patients with <70 years, R0 resections, or treatment with adjuvant chemotherapy. Tumor relapses after surgery and peritoneal spread were significantly higher in the EMT-positive tumors. Conclusions: EMT status, when assessed through immunohistochemistry, identified an aggressive phenotype of MSS diffuse-type tumors with extensive lymph nodal spread, peritoneal dissemination, and worse long-term outcomes.

Extended Lymphadenectomy for Gastric Cancer in the Neoadjuvant Era: Current Status, Clinical Implications and Contentious Issues

“…Following the introduction of molecular classifications [87][88][89], several studies have been conducted to clarify their potential impact in clinical decision-making and treatment of gastric cancer [47,90]. A different prognosis was attributed to the microsatellite instability (MSI) showing the best survival rate, and to the epithelial-mesenchymal transition (EMT) confirming the worst prognosis.…”

Posterior and Para-Aortic (D2plus) Lymphadenectomy after Neoadjuvant/Conversion Therapy for Locally Advanced/Oligometastatic Gastric Cancer

“…Secondly, the lack of a control group limits the analysis of the real clinical impact of the procedure performed. The selection of patients who could benefit from a more extended approach is an important aspect that needs to be confirmed in future studies, as does the impact of the molecular type on the response to preoperative chemotherapy and related outcomes [38,39].…”