Clinicopathologic Significance of TROP2 and Phospho-TROP2 in Gastric Cancer
Abstract Background: Trophoblast cell-surface antigen 2 (TROP2) is a transmembrane glycoprotein expressed in epithelial cells. TROP2 overexpression has been reported to be correlated with malignant progression in most carcinomas, but TROP2 showed a tumor-suppressive function in some types of cancers. We currently developed a novel antibody against phospho-TROP2 (pTROP2). Since the function of TROP2 is controversial, we then aimed to clarify the clinicopathologic significance of TROP2 and pTROP2 expression in human gastric cancer (GC) in this study.Methods: We retrospectively analyzed the cases of 704 GC patients who underwent gastrectomy. The expressions of TROP2 and pTROP2 in each tumor were evaluated by immunohistochemistry. We analyzed the correlation between the GC patients' clinicopathologic features and the TROP2 and pTROP2 expression in their tumors.Results: Overexpression of TROP2 and that of pTROP2 were identified in 330 (46.9%) and 306 (43.5%) of the 704 GC patients, respectively. TROP2 overexpression was significantly correlated with the histological intestinal type, high tumor invasion depth (T3/T4), lymph node metastasis, lymphatic invasion, and venous invasion. In contrast, pTROP2 overexpression was significantly correlated with intestinal type, low tumor invasion depth (T1/2), no lymph node metastasis, and no lymphatic invasion. TROP2 overexpression was significantly associated with poorer overall survival (p<0.01, log rank), whereas pTROP2 overexpression was significantly associated with better overall survival (p<0.01, log rank).Conclusion: TROP2, but not pTROP2, might be associated with the metastatic ability of GC, resulting in poor prognoses for GC patients.